Research Article: Three-dimensional ultrasound imaging of fetal brain fissures in the growth restricted fetus

Date Published: May 23, 2019

Publisher: Public Library of Science

Author(s): Sofie C. Husen, Irene V. Koning, Attie T. J. I. Go, Anne W. van Graafeiland, Sten P. Willemsen, Irene A. L. Groenenberg, Régine P. M. Steegers-Theunissen, Jessica Dubois.


To examine differences in growth trajectories of fetal brain fissures in the growth restricted fetus (FGR) compared to controls.

We selected a subgroup of 227 women with a singleton pregnancy from the Rotterdam Periconceptional Cohort. Participants received three-dimensional ultrasound (3D-US) examinations of the fetal brain at 22, 26 and 32 weeks of gestational age (GA). The left and right Sylvian, insula and parieto-occipital fissures (POF) were measured in standardized planes. Linear mixed models with adjustment for potential confounders were applied to estimate differences between the trajectories of brain fissure depth measurements of FGR and controls.

22 FGR and 172 controls provided 31 and 504 3D-US respectively for longitudinal brain fissure depth measurements. Success rates for the Sylvian and insula depth measurements were over 80% and for POF over 62% at all GA. In FGR compared to controls, the trajectory of the right Sylvian fissure depth was significantly decreased (ß = -4.30, 95%CI = -8.03;-0.56, p = 0.024) while its growth rate was slightly increased (ß = 0.02, 95%CI = 0.00;0.04, p = 0.04), after adjustment for GA, head circumference, gender, educational level and parity.

The small differences in brain fissure measurements between 22 and 32 weeks GA in FGR warrant further investigation in larger cohorts with postnatal follow-up.

Partial Text

Fetal growth restriction (FGR) affects 6–10% of pregnancies [1]. These fetuses are at risk for adverse pregnancy and neurodevelopmental outcomes, such as autism, attention deficit hyperactive disorder and schizophrenia [2, 3]. In FGR the ‘brain sparing effect’, referring to the cerebro-placental blood flow redistribution due to placental insufficiency measured with Doppler ultrasound, causes a change in oxygenation pattern in the fetus [4]. Since abnormal flow and oxygen patterns causing delayed cerebral development have been described in fetuses with congenital heart defects [5, 6], this change in blood flow could indicate an increased risk of developing brain abnormalities and subsequent neurodevelopmental disorders in FGR fetuses [4, 7, 8].

With this explorative study we try to push the boundaries towards a more subtle look at the developing fetus, especially of the brain development in FGR. Not only growth itself, but also brain development seems to be different in this fetuses. We show that subtle measurements in the fetal brain can be performed reliable and seem to be different between FGR and controls already in the second trimester of pregnancy. This should be considered as the first step towards screening FGR fetuses using these 3D ultrasound brain measurements and to perform future research on what will be the consequence of these differences. Improvement of fetal management techniques contributes to a higher survival rate of FGR fetuses with higher rates of childhood morbidity [36]. One of these morbidities associated with FGR is abnormal neurodevelopmental outcome [1, 36]. We argue that identification of fetuses at risk for neurodevelopmental impairment prenatally is essential to improve pre- and postnatal management and define strategies to improve neurodevelopmental outcome. However, replication of our study is essential to investigate whether our method can be used for this purpose in the future. Our results imply the presence of prenatal developmental changes of the brain in in FGR fetuses. However, whether these small regional changes are of clinical relevance for postnatal neurodevelopmental outcome needs to be elucidated. For this purpose studies with a larger sample size to increase power and postnatal follow-up is necessary.