Abstract
In the present study, we compared brain development and metabolism of small-for-gestational-age (SGA) and appropriate-for-gestational-age (AGA) infants using proton magnetic resonance spectroscopy (1H-MRS). We tested the hypothesis that intrauterine growth retardation caused by placental insufficiency is associated with changes in cerebral metabolism and is followed by an adverse neurodevelopmental outcome at the age of 2 y. Twenty-six AGA and 14 SGA (birth weight <P 2.3) preterm infants with no major ultrasound abnormalities were enrolled prospectively. At 32 and 41 wk postmenstrual age, 1H-MRS and magnetic resonance imaging were performed. For 1H-MRS, a volume of interest was placed in the basal ganglia and in the periventricular white matter. Using echo times of 31 and 144 ms N-acetylaspartate/choline (NAA/Cho), lactate/Cho, myo-inositol/Cho (mI/Cho), and glutamate-glutamine-γ-aminobutyric acid/Cho (Glx/Cho) ratios were compared between AGA and SGA groups. Griffiths' developmental quotient (DQ) values were assessed at 24 mo corrected age. Griffiths' DQ (AGA, 104 ± 10; SGA, 99 ± 9) and brain development assessed using magnetic resonance imaging showed no significant differences between both AGA and SGA groups, and NAA/Cho, Lac/Cho, mI/ Cho, and Glx/Cho ratios were not significantly different between the groups. NAA/Cho ratios increased from 32 to 41 wk, whereas mI/Cho ratios decreased in both groups. No differences in cerebral metabolism, brain development, and DQ values between AGA and severely SGA infants could be demonstrated.
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
Abbreviations
- AGA:
-
appropriate for gestational age
- BG:
-
basal ganglia
- Cho:
-
choline
- DQ:
-
developmental quotient
- Glx:
-
glutamate/glutamine/γ-aminobutyric acid
- 1H-MRS:
-
proton magnetic resonance spectroscopy
- Lac:
-
lactate
- mI:
-
myo-inositol
- MRI:
-
magnetic resonance imaging
- NAA:
-
N-acetylaspartate
- NAAG:
-
N-acetylaspartylglutamate
- PVWM:
-
periventricular white matter
- SGA:
-
small for gestational age
- TE:
-
echo time
- TI:
-
inversion time
- TR:
-
repetition time
- VOI:
-
volume of interest
References
Hutton JL, Pharoah PO, Cooke RW, Stevenson RC 1997 Differential effects of preterm birth and small gestational age on cognitive and motor development. Arch Dis Child Fetal Neonatal Ed 76: F75–F81.
Kok JH, den Ouden AL, Verloove-Vanhorick SP, Brand R 1998 Outcome of very preterm small for gestational age infants: the first nine years of life. Br J Obstet Gynaecol 105: 162–168.
Topp M, Langhoff-Roos J, Uldall P, Kristensen J 1996 Intrauterine growth and gestational age in preterm infants with cerebral palsy. Early Hum Dev 44: 27–36.
Wallace IF, McCarton CM 1997 Neurodevelopmental outcomes of the premature, small-for-gestational-age infant through age 6. Clin Obstet Gynecol 40: 843–852.
Reuwer PJ, Sijmons EA, Rietman GW, van Tiel MW, Bruinse HW 1987 Intrauterine growth retardation: prediction of perinatal distress by Doppler ultrasound. Lancet 2: 415–418.
GRIT Study Group, 2003 A randomised trial of timed delivery for the compromised preterm fetus: short term outcomes and Bayesian interpretation. BJOG 110: 27–32.
Groenendaal F, Veenhoven RH, van der Grond J, Jansen GH, Witkamp TD, de Vries LS 1994 Cerebral lactate and N-acetyl-aspartate/choline ratios in asphyxiated full-term neonates demonstrated in vivo using proton magnetic resonance spectroscopy. Pediatr Res 35: 148–151.
Robertson NJ, Cox IJ, Cowan FM, Counsell SJ, Azzopardi D, Edwards AD 1999 Cerebral intracellular lactic alkalosis persisting months after neonatal encephalopathy measured by magnetic resonance spectroscopy. Pediatr Res 46: 287–296.
Peden CJ, Rutherford MA, Sargentoni J, Cox IJ, Bryant DJ, Dubowitz LM 1993 Proton spectroscopy of the neonatal brain following hypoxic-ischemic injury. Dev Med Child Neurol 35: 502–510.
Barkovich AJ, Baranski K, Vigneron D, Partridge JC, Hallam DK, Hajnal BL, Ferriero DM 1999 Proton MR spectroscopy for the evaluation of brain injury in asphyxiated, term neonates. AJNR Am J Neuroradiol 20: 1399–1405.
Roelants-van Rijn AM, van der Grond J, de Vries LS, Groenendaal F 2001 Value of 1H-MRS using different echo times in neonates with cerebral hypoxia-ischemia. Pediatr Res 49: 356–362.
Amess PN, Penrice J, Wylezinska M, Lorek A, Townsend J, Wyatt JS, Amiel-Tison C, Cady EB, Stewart A 1999 Early brain proton magnetic resonance spectroscopy and neonatal neurology related to neurodevelopmental outcome at 1 year in term infants after presumed hypoxic-ischaemic brain injury. Dev Med Child Neurol 41: 436–445.
Isaacks RE, Bender AS, Kim CY, Prieto NM, Norenberg MD 1994 Osmotic regulation of myo-inositol uptake in primary astrocyte cultures. Neurochem Res 19: 331–338.
Kreis R, Ernst T, Ross BD 1993 Development of the human brain: in vivo quantification of metabolite and water content with proton magnetic resonance spectroscopy. Magn Reson Med 30: 424–437.
Robertson NJ, Lewis RH, Cowan FM, Allsop JM, Counsell SJ, Edwards AD, Cox IJ 2001 Early increases in brain myo-inositol measured by proton magnetic resonance spectroscopy in term infants with neonatal encephalopathy. Pediatr Res 50: 692–700.
Hagberg H, Thornberg E, Blennow M, Kjellmer I, Lagercrantz H, Thiringer K, Hamberger A, Sandberg M 1993 Excitatory amino acids in the cerebrospinal fluid of asphyxiated infants: relationship to hypoxic-ischemic encephalopathy. Acta Paediatr 82: 925–929.
Groenendaal F, Roelants-van Rijn AM, van der Grond J, Toet MC, de Vries LS 2001 Glutamate in cerebral tissue of asphyxiated neonates during the first week of life demonstrated in vivo using proton magnetic resonance spectroscopy. Biol Neonate 79: 254–257.
Nguyen L, Rigo JM, Rocher V, Belachew S, Malgrange B, Rogister B, Leprince P, Moonen G 2001 Neurotransmitters as early signals for central nervous system development. Cell Tissue Res 305: 187–202.
Levene MI, de Crespigny LC 1983 Classification of intraventricular hemorrhage. Lancet 1: 643
de Vries LS, Eken P, Dubowitz LM 1992 The spectrum of leukomalacia using cranial ultrasound. Behav Brain Res 49: 1–6.
Kloosterman GJ 1969 Intrauterine growth and intrauterine growth curves. Maandschrift voor Kindergeneeskunde 37: 209–225.
Griffiths R 1976 The Abilities of Babies: A Study in Mental Measurement. Amersham, Bucks
Groenendaal F, Leusink C, Nijenhuis M, Janssen MJ 2002 Neonatal life support during magnetic resonance imaging. J Med Eng Technol 26: 71–74.
Battin M, Rutherford MA 2002 Magnetic resonance imaging of the brain in preterm infants: 24 weeks' gestation to term. In: Rutherford MA (ed) MRI of the Neonatal Brain. Saunders, London, pp 25–49.
Naressi A, Couturier C, Castang I, de Beer R, Graveron-Demilly D 2001 Java-based graphical user interface for MRUI, a software package for quantitation of in vivo/ medical magnetic resonance spectroscopy signals. Comput Biol Med 31: 269–286.
Urenjak J, Williams SR, Gadian DG, Noble M 1993 Proton nuclear magnetic resonance spectroscopy unambiguously identifies different neural cell types. J Neurosci 13: 981–989.
Martin E, Capone A, Schneider J, Hennig J, Thiel T 2001 Absence of N-acetylaspartate in the human brain: impact on neurospectroscopy?. Ann Neurol 49: 518–521.
Bjartmar C, Battistuta J, Terada N, Dupree E, Trapp BD 2002 N-acetylaspartate is an axon-specific marker of mature white matter in vivo: a biochemical and immunohistochemical study on the rat optic nerve. Ann Neurol 51: 51–58.
Patel TB, Clark JB 1979 Synthesis of N-acetyl-L-aspartate by rat brain mitochondria and its involvement in mitochondrial/cytosolic carbon transport. Biochem J 184: 539–546.
Truckenmiller ME, Namboodiri MA, Brownstein MJ, Neale JH 1985 N-Acetylation of L-aspartate in the nervous system: differential distribution of a specific enzyme. J Neurochem 45: 1658–1662.
van der Knaap MS, van der Grond J, van Rijen PC, Faber JA, Valk J, Willemse K 1990 Age-dependent changes in localized proton and phosphorus MR spectroscopy of the brain. Radiology 176: 509–515.
Kreis R, Hofmann L, Kuhlmann B, Boesch C, Bossi E, Huppi PS 2002 Brain metabolite composition during early human brain development as measured by quantitative in vivo 1H magnetic resonance spectroscopy. Magn Reson Med 48: 949–958.
Kimura H, Fujii Y, Itoh S, Matsuda T, Iwasaki T, Maeda M, Konishi Y, Ishii Y 1995 Metabolic alterations in the neonate and infant brain during development: evaluation with proton MR spectroscopy. Radiology 194: 483–489.
Hüppi PS, Fusch C, Boesch C, Burri R, Bossi E, Amato M, Herschkowitz N 1995 Regional metabolic assessment of human brain during development by proton magnetic resonance spectroscopy in vivo and by high-performance liquid chromatography/gas chromatography in autopsy tissue. Pediatr Res 37: 145–150.
Pu Y, Li QF, Zeng CM, Gao J, Qi J, Luo DX, Mahankali S, Fox PT, Gao JH 2000 Increased detectibility of alpha brain glutamate/glutamine in neonatal hypoxic-ischemic encephalopathy. AJNR Am J Neuroradiol 21: 203–212.
Leth H, Toft PB, Pryds O, Peitersen B, Lou HC, Henriksen O 1995 Brain lactate in preterm and growth-retarded neonates. Acta Paediatr 84: 495–499.
Cady EB, Penrice J, Amess PN, Lorek A, Wylezinska M, Aldridge RF, Franconi F, Wyatt JS, Reynolds EO 1996 Lactate, N-acetylaspartate, choline and creatine concentrations, and spin-spin relaxation in thalamic and occipito-parietal regions of developing human brain. Magn Reson Med 36: 878–886.
Sanchez-Abarca LI, Tabernero A, Medina JM 2001 Oligodendrocytes use lactate as a source of energy and as a precursor of lipids. Glia 36: 321–329.
Acknowledgements
We thank the technicians Cheraar Leusink and Marco Nijenhuis for testing the equipment and all other technicians of the MRI institute for their enthusiastic cooperation. The MRUI software package was kindly provided by the participants of the EU Network programs: Human Capital and Mobility (CHRX-CT94-0432) and Training and Mobility of Researchers (ERB-FMRX-CT970160). We thank our colleagues Corine Koopman-Esseboom and Inge-Lot van Haastert for help with the follow-up examinations.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Roelants-van Rijn, A., van der Grond, J., Stigter, R. et al. Cerebral Structure and Metabolism and Long-Term Outcome in Small-for-Gestational-Age Preterm Neonates. Pediatr Res 56, 285–290 (2004). https://doi.org/10.1203/01.PDR.0000132751.09067.3F
Received:
Accepted:
Issue date:
DOI: https://doi.org/10.1203/01.PDR.0000132751.09067.3F
This article is cited by
-
Brain proton magnetic resonance spectroscopy and neurodevelopment after preterm birth: a systematic review
Pediatric Research (2022)
-
The long-term effect of erythropoiesis stimulating agents given to preterm infants: a proton magnetic resonance spectroscopy study on neurometabolites in early childhood
Pediatric Radiology (2018)
-
Magnetic resonance spectroscopy in very preterm-born children at 4 years of age: developmental course from birth and outcomes
Neuroradiology (2018)
-
Brain metabolite concentrations are associated with illness severity scores and white matter abnormalities in very preterm infants
Pediatric Research (2013)
-
Neuroimaging biomarkers of preterm brain injury: toward developing the preterm connectome
Pediatric Radiology (2012)
