Abstract 15082: Altered Functional Brain Circuitry in Fetuses With Complex Congenital Heart Disease

Recent reports describing regional alterations involving critical hubs of the developing brain have emerged in neonates with complex CHD prior to surgery. However, the extent to which postnatal brain connectivity disturbances reflect a prenatal onset of aberrant functional circuitry development is unknown. Here, we investigated whether neural connectivity changes are present in fetuses with CHD before birth. We acquired 176 resting state scans from 156 pregnant women who were prospectively enrolled. We analyzed 76 scans from 61 CHD fetuses (mean±sd:33.4±3.1 gestational weeks, GW); which included transposition of the great arteries, n=22; hypoplastic left heart syndrome, n=20; other CHD, n=34) and 103 scans from 95 healthy controls (33.8±3.3 GW). First, we defined 98 anatomic regions ( nodes ) using a fetal atlas. Next, for each fetus, we computed connectivity – the pairwise Fisher- z transformed Pearson correlation, ( z(r) ) – across all 98 nodes. Only the strongest 4% of connections, or 190 edges , were included. Next, we grouped nodes into 16 clusters, or modules , based on a node’s connectivity to other nodes. We then compared (1) the number of connections within ( w-edges ) and between ( b-edges ) modules, and (2) the strength of connectivity within ( w-strength ) and between ( b-strength ) modules. We expected 12/190 w-edges and 177/190 b-edges but observed 55 and 54 w-edges in healthy (H) and CHD fetuses, respectively, 4.5x greater than the expected. Thus, in both cohorts, the normalized w-edges were significantly greater than the normalized b-edges ( p < 0.001); there were no significant between-group differences. However, w-strength (H,1.16±0.26; CHD, 1.14±0.31) and b-strength (H, 1.05±0.19; CHD, 1.04±0.26) were significantly reduced in CHD ( p <0.001). In both, w-strength was greater than b-strength (p<0.001). For the first time, we demonstrated that CHD functional networks follow normative trajectories where within-module connectivity predominates, both in strength and number, in-utero. Fetal CHD connectivity strength, however, was weaker compared to controls suggesting that altered functional brain circuitry in CHD has its origins in-utero. Further studies are needed to assess the surveillance and prognostic potential of these findings.