Association of Isolated Congenital Heart Disease with Fetal Brain Maturation

Abstract

Background and purpose: Brain MRI of newborns with congenital heart disease show signs of immaturity relative to healthy controls. Our aim was to determine whether the semiquantitative fetal total maturation score can detect abnormalities in brain maturation in fetuses with congenital heart disease in the second and third trimesters.

Materials and methods: We analyzed data from a prospective study of fetuses with and without congenital heart disease who underwent fetal MR imaging at 25-35 weeks' gestation. Two independent neuroradiologists blinded to the clinical data reviewed and scored all images using the fetal total maturation score. Interrater reliability was evaluated by the intraclass correlation coefficient using the individual reader scores, which were also used to calculate an average score for each subject. Comparisons of the average and individual reader scores between affected and control fetuses and relationships with clinical variables were evaluated using multivariable linear regression.

Results: Data from 69 subjects (48 cardiac, 21 controls) were included. High concordance was observed between readers with an intraclass correlation coefficient of 0.98 (95% CI, 0.97-0.99). The affected group had significantly lower fetal total maturation scores than the control group (β-estimate, -0.9 [95% CI, -1.5 to -0.4], P = .002), adjusting for gestational age and sex. Averaged fetal total maturation, germinal matrix, myelination, and superior temporal sulcus scores were significantly delayed in fetuses with congenital heart disease versus controls (P < .05 for each). The fetal total maturation score was not significantly associated with any cardiac, anatomic, or physiologic variables.

Conclusions: The fetal total maturation score is sensitive to differences in brain maturation between fetuses with isolated congenital heart disease and healthy controls.

Fig 1.

Bland-Altman plot demonstrating high interrater reliability. The overall mean difference between readers was 0.01 (95% CI, 0.14–0.17).

Fig 2.

Differences in fTMS values between a control subject and a fetus in the second trimester. A–C, Multiplanar reformatted images from a 26-week 6-day-old control fetus with an fTMS of 6.5 shows early development of the right superior temporal sulcus (A, B, and C; arrow) and early myelination in the thalamus and posterior limb of the internal capsule (C, dotted arrow). D–F, Multiplanar reformatted images from a 26-week 6-day-old fetus with hypoplastic left-heart syndrome with an fTMS of 4 show a smooth temporal lobe (absent superior temporal sulcus) and lack of myelination.

Fig 3.

Differences in fTMS between a control subject and a subject with CHD in the third trimester. A–C, Multiplanar reformatted images from a 30-week 6-day-old control fetus with an fTMSav of 14 show early insular sulcation (A, dotted arrow), a developing inferior temporal sulcus (B, solid arrow), and no residual germinal matrix (C). D–F, Multiplanar reformatted images from a 31-week 2-day old fetus with tricuspid atresia and an fTMS of 10 show a smooth insula (D), no evidence of a developing inferior temporal sulcus (E), and some residual germinal matrix (F, arrowhead).

Fig 4.

Scatterplot illustrating the estimated delay in fTMSav values in fetuses with CHD compared with controls. Lines are predicted fTMSav scores modeled by linear regression.

Fig 5.

Scatterplot illustrating the estimated delay in averaged germinal matrix subscores in fetuses with CHD compared with controls. Lines are predicted averaged germinal matrix scores modeled by ordinal logistic regression.