Biochemical maturation of the brain can be studied noninvasively by 1 H magnetic resonance spectroscopy (MRS) in human infants. Detailed time courses of cerebral tissue contents are known for the most abundant metabolites only, and whether or not premature birth affects biochemical maturation of the brain is disputed. Hence, the last trimester of gestation was observed in infants born prematurely, and their cerebral metabolite contents at birth and at expected term were compared with those of fullterm infants. Successful quantitative short-TE 1 H MRS was performed in three cerebral locations in 21 infants in 28 sessions (gestational age 32-43 weeks). The spectra were analyzed with linear combination model fitting, considerably extending the range of observable metabolites to include acetate, alanine, aspartate, cholines, creatines, ␥-aminobutyrate, glucose, glutamine, glutamate, glutathione, glycine, lactate, myo-inositol, macromolecular contributions, N-acetylaspartate, N-acetylaspartylglutamate, o-phosphoethanolamine, scyllo-inositol, taurine, and threonine. Significant effects of age and location were found for many metabolites, including the previously observed neuronal maturation reflected by an increase in N-acetylaspartate. Absolute brain metabolite content in premature infants at term was not considerably different from that in fullterm infants, indicating that prematurity did not affect biochemical brain maturation substantially in the studied population, which did not include infants of extremely low birthweight. Magn Reson Med 48:949 -958, 2002.

Postnatal brain development of healthy prematurely born infants was assessed to study possible influence of premature birth and early extrauterine environment on structural, biochemical, and functional brain development. Myelination and differentiation of gray and white matter were studied by in vivo magnetic resonance (MR) imaging (MRI), changes in cerebral metabolism by 1HMR spectroscopy (MRS), and changes in early human neurobehavior by the assessment of preterm infant's behavior (APIB). The stage of intrauterine and extrauterine brain development in prematurely born infants at term was compared with the stage of mainly intrauterine brain development in a group of full-term infants. Eighteen preterm infants unremarkable with respect to neurologic and medical status were studied at approximately 2 wk of postnatal age [gestational age (GA) 1: 32.5 +/- 1.2 wk] and again at term (GA 2: 40.0 +/- 1.1 wk). For comparison a group of 13 full-term born infants (GA T: 40.6 +/- 2.1 wk) were studied by MR and six by APIB. When GA 2 to GA 1 was compared, significant maturational changes were found with MRI in gray and white matter and myelination, with 1H MRS in the concentration of N-acetylaspartate and with all scores of APIB. In preterm infants at term (GA 2) compared with full-term infants (GA T) significantly less gray and white matter differentiation and myelination was observed as well as significantly poorer performance in four neurobehavioral parameters (autonomic reactivity, motoric reactivity, state organization, attentional availability). We conclude that MRI and 1H MRS can be used to study postnatal brain development in preterm infants. Structural and biochemical maturation is accompanied by functional maturation as shown with the neurobehavior assessment. Preterm infants at term compared with full-term infants show a structural as well as a functional delay in brain development assessed at 40 wk of postconceptional age.

Localized proton magnetic resonance spectra were recorded from human cerebellum in vivo with a 1.5-T magnet. The spectra from healthy adults and preterm and term babies showed resonances from N-acetylaspartate, creatine and phosphocreatine, choline-containing compounds such as phosphocholine and glycerophosphocholine, taurine, and inositol. The age-dependent changes of in vivo molar concentrations of N-acetylaspartate, choline, taurine, and inositol were estimated in preterm babies, babies at term, and adults. The range of postconceptional age in the studied babies was 31 to 45 wk. Taking the biochemically measured creatine concentrations in age-corresponding autopsy material as an internal standard, the in vivo concentrations of the other metabolites were calculated from the proton spectra. N-acetylaspartate showed an increase from 1.9 mM in preterm babies to 3.1 mM in term babies and to 6.5 mM in adult brain. Taurine was noted to increase from 1.1 mM in preterm infants to 2.3 mM in term infants and did not decrease significantly in adult brain. Choline and inositol concentrations did not change significantly throughout the studied age groups. These new data on in vivo, localized 1H-spectroscopy show that it is a sensitive method for studying early metabolic brain development in humans.

To study the course of regional metabolite concentrations during early brain development, we measured in vivo metabolites [N-acetyl-aspartate (NAA), choline-containing compounds, and myoinositol (M-Ino)] in the precentral area of the cerebrum by short echo-time single volume proton magnetic resonance spectroscopy and compared in vivo established spectroscopic data with classic chromatographic data (HPLC) on age-corresponding autopsy tissue in different regions of the brain. In autopsy tissue, regional (frontal lobe, precentral area, basal ganglia, thalamus) and age-dependent differences of the concentration of creatine, NAA, and M-Ino were determined. In vivo measurement of NAA by proton magnetic resonance spectroscopy shows a significant increase of NAA by increasing postconceptional age. M-Ino shows a weak correlation and a nonsignificant decrease with increasing postconceptional age. Choline shows no age-dependent changes. Creatine concentrations measured by HPLC in different regions of the developing brain at autopsy showed an age-dependent increase that was identical for the left and right side and similar for the precentral area and frontal lobe and more pronounced for the basal ganglia and thalamus. Comparison of the results obtained by the two methods shows agreement for the age-dependent changes and the absolute concentration of M-Ino. NAA determined in autopsy tissue by HPLC is significantly lower than that measured in vivo by proton magnetic resonance spectroscopy. A comparison of the concentrations measured by HPLC in frontal lobe, basal ganglia, and thalamus with the results obtained from the precentral area showed significant regional differences in all measured metabolites. These results define important age-dependent changes detected with both methods and further indicate limitations of both methods that have to be considered when presenting absolute concentration values.

This review deals with retinopathy of prematurity (ROP), a disease characterized by retinovitreal neovascularization, eventually retinal detachment and blindness. Due to the increasing number of extremely premature newborns, it is becoming more frequent. ROP of all stages occurs in 25-35% of surviving premature newborns of gestational age up to approximately 35 weeks. Stages 3 or more occur in 5-10%, blindness in 3-5% of very immature babies. The incidence is inversely related to gestational age. Classification is internationally unified (ICROP) and describes 5 stages. Its pathogenesis has not yet been clarified. More or less proven risk factors are retinovascular immaturity, hyperoxia and possibly circulatory and respiratory instability. Prophylaxis consists in avoiding hyperoxia, and probably also in keeping the extremely premature newborn stable. Ophthalmologic examinations must be performed by ophthalmologists experienced in this field or under their direct responsibility and must be standardized. Treatment of ROP can be carried out at a certain stage by coagulation therapy.