Quantitative assessment of cerebral metabolism and hemodynamics in small-for-gestational-age (SGA) newborns

Background: Small-for-gestational-age (SGA) newborns represent approximately 10% of births worldwide and 45% of births in some countries. It has been suggested that SGA might cause learning difficulties and behavioral abnormalities in childhood, yet the neurobiological basis for this is poorly understood. In this study, we employed several advanced imaging techniques-including T2-relaxation-under-spin-tagging (TRUST) magnetic resonance imaging (MRI), and phase-contrast (PC) MRI-to quantify oxygen extraction fraction (OEF), global cerebral blood flow (CBF), and cerebral metabolic rate of oxygen (CMRO2) to elucidate pathophysiological vulnerabilities of SGA neonates. Methods: A total of 41 newborns were enrolled in this study, consisting of 29 SGA and 12 appropriate for-gestational-age (AGA) neonates. The SGA group was further divided into subgroups with and without abnormalities on structural MRI, denoted as SGA-a (N=17) and SGA-n (N=12). TRUST and PC MRI were performed to determine OEF, CBF, and CMRO2. Linear regression analyses were performed to examine physiological parameters' dependence on scan age, gender, and group. Similar analyses were conducted for birth weight and brain volume. Receiver operating characteristic (ROC) curves were used to test physiological parameters' ability to different diagnostic groups. Results: Regression analysis revealed that CMRO2 was significantly lower (P=0.04) in the SGA group relative to the AGA group. When further stratifying the SGA participants into SGA-a and SGA-n subgroups, the SGA-a subgroup was found to have the most pronounced physiological deficits, with a lower CMRO2 (P=0.004) and lower CBF (P=0.007) than those in the AGA group. Conversely, CMRO2 (P=0.40) and CBF (P=0.90) in the SGA-n subgroup were not different from those of the AGA group. Accordingly, CBF in the SGA-a group was significantly lower (P=0.01) than that of the SGA-n group and CMRO2 also showed a difference (P=0.09). Additionally, CMRO2 (P=0.002) and CBF (P=0.04) showed an age-related increase during this early developmental period. In analyzing the SGA-a subgroup relative to the remaining neonates, the area under curve (AUC) values were 0.6, 0.6, 0.7, 0.8, and 0.5 for birth weight, OEF, CMRO2, CBF, and brain volume, respectively. In analyzing the SGA-a subgroup relative to the SGA-n subgroup, AUC values were 0.5, 0.6, 0.7, 0.8, and 0.5 for birth weight, OEF, CMRO2, CBF, and brain volume. Conclusions: Structural damage in SGA-a neonates is associated with cerebral hemodynamic and metabolic deficits. SGA neonates with normal CBF and CMRO(2)reveal minimal structural abnormalities. Physiological imaging may help identify SGA patients at high risk of developing irreversible brain damage.