534 - Altered Fetal Brain Biochemistry in Growth-Restricted Pregnancies

Poster Number: 534
Publication Number: 534.139

Alexander Daigle, Children's National Health System, Washington, DC, United States; Subechhya Pradhan, Children's National Hospital, Washington, DC, United States; Yushuf Sharker, Nationwide Children's Hospital, Washington, DC, United States; Jessica Quistorff, Children's National Health System, Washington, DC, United States; Homa K. Ahmadzia, GW, Washington, DC, United States; Kushal Kapse, Developing Brain Institute, Washington, DC, United States; Catherine Limperopoulos, Children's National Health System, Washington, DC, United States; Nickie Andescavage, Children's National Health System, Washington, DC, United States

Background: Placental insufficiency can result in fetal growth restriction (FGR), which is associated with neuro-developmental morbidity. Mechanisms of brain injury remain unclear and difficult to detect in utero.

Objective: To compare fetal brain biochemical profiles between healthy and FGR-affected pregnancies using proton magnetic resonance imaging (1H-MRS).

Design/Methods: We prospectively enrolled pregnant women with established FGR (EFW < 10th centile) and healthy controls with normal prenatal screening studies. Fetal MRI studies were obtained using a 1.5 Tesla MR scanner. 1H-MRS acquisitions were acquired from the central brain of the fetus with an echo-time of 144ms. After undergoing frequency and phase corrections, spectra were quantified using LCModel analysis software, and metabolite concentrations of N-acetylaspartate (NAA), choline (Ch), creatine (Cr), myo-inositol (Ins), scyllo-inositol (Scyllo), lactate (Lac) and NAA:Ch ratios were estimated using water spectrum as an internal reference. We evaluated group differences in metabolic outcomes between groups adjusting for maternal age, gestational age at study and fetal sex.

Results: We studied 227 fetuses (44 FGR, 183 controls) at a mean gestational age (GA) of 32.2 weeks for FGR (range 22.0 – 38.6 weeks) and 31.8 weeks for controls (range 23.6 – 39.4 weeks) (Table 1). Concentrations of cerebral scyllo were significantly higher in FGR compared to controls (FGR = 0.475 IU ± 0.158; controls = 0.38 IU ± 0.134, p < 0.001), while NAA:Ch ratios were significantly lower in FGR compared to that of controls (FGR=1.18 IU ± 0.320; controls=1.41 IU ±0.465, p < 0.01) (Figure 1). No statistically significant differences were found for the other metabolites (Figure 2).Conclusion(s): We report significant differences in fetal cerebral metabolite concentrations between FGR-affected and healthy pregnancies. Inositols are associated with glucose homeostasis and in the brain are associated with altered glial and neuronal metabolism. Fetal trajectories of NAA as well as NAA:Ch ratios increase significantly in the third trimester, reflective of early myelination and dendritic-synaptic proliferation. These alterations in FGR may reflect disrupted fetal metabolism in response to placental insufficiency and may contribute to later neurodevelopmental delays. Clinical implications of these findings warrant further evaluation and long-term neurodevelopmental follow-up is underway.   
Table 1Analytical summary of metabolites between the control group and FGR group. Difference estimates are adjusted for the scan time, maternal age, gestational age, and fetal sex.
Figure 1Metabolites which are different between control and FGR groups. Lower edge of the box represents the 1st quartile or Q1, the upper end of the box represents the 3rd quartile or Q3, and the horizontal line in the middle of the box represents the median Q2. The lower whisker limit is calculated as Q1 – 1.5*(Q3-Q1) and the upper whiskers limit is calculated as Q3 + 1.5*(Q3-Q1). Data outside the whiskers range were considered as outliers.