672 - Relationship of Clinical Co-morbidities with the Altered Maturational Trajectory of Cerebral Metabolites in Preterm Infants

Publication Number: 2655.672

Anola Stage, Children's National Health System, Washington, DC, United States; Katherine Ottolini, George Washington University School of Medicine and Health Sciences, Washington, DC, United States; Julius Ngwa, Children's National Health System, Washington, DC, United States; Jonathan Murnick, Children's National Health System, Washington, DC, United States; Sudeepta Basu, Children's National Health System, Washington, DC, United States; Kushal Kapse, Developing Brain Institute, Washington, DC, United States; Nickie Andescavage, Children's National Health System, Washington, DC, United States; Catherine Limperopoulos, Children's National Health System, Washington DC, DC, United States

Background: The latter half of pregnancy is a critical period of rapid fetal brain growth and maturation. Preterm birth is an abrupt cessation of the supportive in-utero environment and directly impacts neurodevelopment. Magnetic resonance spectroscopy (MRS) provides a non-invasive method to evaluate development at the biochemical level and its perturbations after preterm birth.

Objective: To characterize the relationship of clinical comorbidities with maturational cerebral metabolite trajectories in preterm infants.

Design/Methods: Preterm neonates born ≤36-weeks gestational age (wga) without moderate-severe structural brain injury, genetic or metabolic disorder, perinatal infection, or birth weight < 10th percentile, were prospectively enrolled. Serial non-sedated brain magnetic resonance imaging (MRI) on a 1.5 Tesla scanner and MRS with voxel located above the cingulate cortex (TR=1500; TE=144ms) were performed approximately every 4 weeks (Figure 1). Individual metabolite concentrations were reported in water-scaled institutional units. Maturational trajectories for cerebral metabolites were analyzed for their relationship with prematurity-related clinical comorbidities using a random intercept linear mixed effects model adjusting for postmenstrual age at the time of the scan, sex, and social vulnerability index. Significance threshold was set at p < 0.008 to adjust for multiple comparisons.

Results: 1H-MRS data were acquired for 153 preterm subjects encompassing 247 MRI scans, with a maximum of 3 scans per subject. The average gestational age at birth and at the time of first scan was 28.56wga and 32.06wga, respectively. The average birth weight was 1179g with 52% female sex (Table 1). Of the clinical covariates assessed, only the presence of a moderate-to-large patent ductus arteriosus (PDA) was significantly associated with brain metabolite maturation, specifically on the trajectory for total N-acetylaspartate (tNAA;β=-0.48, SE=0.16, p=0.003) (Table 2a, b).

Conclusion(s): tNAA, a marker of neuronal activity, increases rapidly with increasing brain maturity in the 3rd trimester, while a declining level has been correlated with neuronal loss and cerebral injury. The observed negative relationship between levels of tNAA and a moderate-to-large PDA in these preterm infants suggests altered brain biochemical development is due to the differences in circulation and oxygenation. Our observations continue to underscore the need for further investigation of neuroprotective strategies like optimal nutrition and hemodynamic monitoring to support the normal biochemical maturation of the brain after preterm birth.

Figure 1: MRS Spectrum of a Preterm Infant
MRS spectrum depiction of a preterm neonate born at 36wga with scan obtained at 38.4wga.

Table 1: Baseline Descriptive Statistics
1H-MRS data were acquired for 153 preterm subjects with the following descriptive statistics and comorbidities.

Table 2: MR Spectroscopy Levels and Preterm Comorbidity Relationship
Maturational trajectories for cerebral metabolites were analyzed for their relationship with prematurity-related clinical comorbidities using a random intercept linear mixed effects model adjusting for postmenstrual age at the time of the scan, sex, and social vulnerability index. Significance threshold was set at p <0.008 to adjust for multiple comparisons. A moderate-large patent ductus arteriosus was significantly associated with total N-acetylaspartate (tNAA).