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Longitudinal Brain and Body Growth in Fetuses With and Without Transposition of the Great Arteries.

Circulation. 2018;138:1368–1370. DOI: 10.1161/CIRCULATIONAHA.118.034467 1368 Adverse neurodevelopment is consistently reported in patients with transposition of the great arteries (TGA).1 In fetuses with TGA, the brain receives mainly substrate-deficient blood returning from the venous system. Our aim was to investigate longitudinal brain and body volume development in fetuses with isolated TGA. We hypothesized that an asymmetrical fetal brain/body growth is initiated early in pregnancy because the circulation in fetuses with TGA is already disrupted in the first trimester. We prospectively included pregnant women with fetuses diagnosed with isolated TGA and controls with normal firstand second-trimester scans. No cases or controls smoked or had diabetes mellitus, hypertension, or previous birthweight <2500 g. We measured total brain volume, cerebellar volume, intracranial cavity volume, and total fetal volume by quantitative volumetric MRI every fourth week from approximately gestational week 24 until delivery. We used a 1.5 Tesla MRI scanner (Avanto) and a 14-second 3D-SSFP sequence with acquisition parameters: echo time 1.74 ms, repetition time 3.99 ms, field of view 40×325×208 mm, spatial resolution 1.6×2.0×3.2 mm (interpolated to 0.8×0.8×2.0 mm3), and acceleration factor 4. MRI volumes were achieved by manual segmentation in Mimics (Materialise). Volumes at the initial scan were analyzed by linear regression analysis adjusted for sex and gestational age. For repeated measures, comparisons were made by linear mixed models, including fixed effects of TGA, gestational age, and sex with random intercept and slope. Contrasts were set at each completed week from gestational weeks 23 to 38. Statistical analysis was performed using Stata. The study was approved by the institutional review committees, and all participants gave written informed consent. Five fetuses with TGA and 11 controls had on average 4.2 MRI scans each (range 3–5) from gestational weeks 22.7 to 38.9 resulting in 67 MRI scans. Groups were similar regarding maternal age, body mass index, and birth weight. Examples of MRI volumes and fetal growth charts are shown in the Figure. The brain/body ratio was significantly lower, and the cerebellar/total brain ratio was significantly higher in cases compared with controls at the initial scan (mean gestational week 24.4, range 22.7–25.9) with P=0.002 and P=0.02, respectively. These significant findings persisted from gestational weeks 23 to 38 (P value at each week <0.005). The brain/intracranial cavity ratio was significantly lower in scans after 30 weeks (P value at each week <0.05). Total brain volume was significantly lower after gestational week 26 (P value at each week <0.01), and intracranial cavity volume was lower between gestational weeks 26 and 33 (P values ≤0.05). We found no significant differences regarding cerebellar volume or total fetal volume at any time during pregnancy. This study presents the first individual, longitudinal growth charts of brain and body volume development in fetuses with TGA compared with controls and proDitte E.S. Jørgensen, MD Ann Tabor, MD, DMedSci Line Rode, MD, PhD Liv Dyre, MD Charlotte K. Ekelund, MD, PhD Signe G. Hellmuth, MD Christopher K. Macgowan, PhD Lone N. Nørgaard, MD Mike Seed, MBBS Karin Sundberg, MD, DMedSci Kirsten Søgaard, MD Lisa N. Jensen, MD Niels Vejlstrup, MD, PhD