Fetal insular measurements in pregnancy with estimated fetal weight <10th centile and childhood neurodevelopmental outcomes.

BACKGROUND: A growing body of evidence suggests that fetal growth restriction is associated with changes in brain structures as a result of chronic hypoxia. However, less is known about the effects of growth-restriction on the fetal insula, particularly in less severely affected late-onset growth restricted fetuses.

OBJECTIVE: This study sought 1) to compare sonographic insular measurements between fetal-growth-restricted, small-for-gestational-age, and appropriate-for-gestational-age control fetuses and 2) to evaluate the association of sonographic insular measurements with perinatal and neurodevelopmental outcomes in fetuses categorized as fetal-growth-restricted or small-for-gestational-age.

STUDY DESIGN: This was a cohort study of singleton non-anomalous pregnancies with an estimated fetal weight <10th centile. Using data from the last examination prior to delivery, fetal insular depth, sylvian fissure depth, hypoechoic insular zone thickness, circumference, and area were measured. All measurements were adjusted for by head circumference. Neurodevelopmental outcomes were evaluated between 2-3 years of age using the Bayley-III scales. Kruskal Wallis H tests were performed to compare insular measurements between groups. Paired t-tests were used to compare insular measurements of appropriate-for-gestational-age fetuses with gestational age-matched growth-restricted fetuses. Insular measurements for patients with and without an adverse perinatal outcome were compared using independent samples t-tests. Spearman correlations were performed to evaluate the relationship of insular measurements to the percentile scores for each of the five Bayley-III subscales and to a summative percentile of these subscales.

RESULTS: A total of 89 pregnancies were included in the study. Sixty-eight of those pregnancies had an estimated fetal weight <10th percentile (fetal-growth-restricted: n=39, small-for-gestational-age: n=29). The appropriate-for-gestational-age cohort consisted of 21 pregnancies. The gestational age at measurement was similar between fetal-growth-restricted and small-for-gestational-age groups, but lower in the appropriate-for-gestational-age group. Differences between groups were noted in normalized insular depth, sylvian fissure depth, and hypoechoic insular zone (p<0.01). Normalized insular depth and hypoechoic insular zone circumference were larger in the growth-restricted cohorts (p<0.01). Normalized sylvian fissure depth was smaller in growth-restricted cohorts (p<0.01). There were no significant differences in insular measurements in pregnancies with and without an adverse perinatal outcome. Bayley-III results were available in 32 of the growth-restricted cases. Of all insular measurements, hypoechoic insular zone circumference was inversely correlated with the adaptive behavior Bayley-III score.

CONCLUSIONS: In our cohort, fetuses with estimated fetal weight <10th percentile have smaller sylvian fissure depths, and larger insular depths and hypoechoic insular zone circumferences than normally growth controls. A larger hypoechoic insular zone circumference was significantly correlated with worse neurodevelopmental outcomes in early childhood. We speculate that enlargement of this region may be an indication of accelerated neuronal maturation in growth-restricted fetuses with mild hypoxia.