Association of Corpus Callosum Development With Fetal Growth Restriction and Maternal Preeclampsia or Gestational Hypertension

This case-control study evaluates the neurodevelopmental and perinatal outcomes in offspring of pregnant individuals with preeclampsia or gestational hypertension.

© 2022 Zheng W et al. JAMA Network Open. two senior radiologists (W.Z., X.Z. with 9 years of fetal MRI experience) using Digital Imaging and Communications in Medicine viewer software (RadiAnt DICOM viewer 2020.2;Medixant, Poznan, Poland). CC length was measured from the most anterior part of the genu to the most posterior part of the splenium tracing a straight rostrocaudal line between the two points, known as the outer-to-outer CC length. CC thickness was measured in its anterior, middle and posterior portions corresponding to the genu, body and splenium thickness, respectively. The thickness of the genu was measured from the most anterior point of the CC to the most anterior point of the inner convexity of the genu; the body thickness was defined as the width of the midcallosum; the splenium thickness is the length of the maximal perpendicular between two parallel lines drawn as tangents to the superior and inferior surfaces of the splenium.
CC morphometry was assessed by measuring the total area and the area of a subdivision in five portions: anterior third, anterior midbody, posterior midbody, isthmus, and splenium region, as described by Witelson et al. 4 . The line of CC length was used as the linear axis to subdivide the CC into anterior and posterior halves; anterior, middle, and posterior thirds; and the posterior one-fifth region. The anterior third region of the CC was defined as the anterior one-third. The anterior midbody region of the CC was defined as the anterior half minus the anterior one-third. The posterior midbody region of the CC was defined as the posterior half minus the posterior one-third. The isthmus region was defined as the posterior one-third minus the posterior one-fifth. The splenium region of the CC was defined as the posterior one-fifth.

Diffusion-weighted imaging analysis: apparent diffusion coefficient (ADC) measurement of the CC
All of the fetal DWI sequences were stored and transferred to the vendor-supplied Advantage Workstation (ADW 4.6 version, GE, USA) for centralized analysis performed separately by two investigators (W.Z., X.Z.). ADC measurements of the CC were based upon regions of interests (ROIs) that were previously reported in the literature 5 . Manual placement of the ROIs was carried out on DWI sequence with the axial plane on internal capsule layer, superior to inferior direction, and referred to the histological and MRI fetal brain atlases. The signal intensity was measured in two ROIs, including the anterior third region (ROI 1) and the splenium region (ROI 2) of the CC. The dimension of each ROI was 15-20 mm 2 at less than 32 weeks of gestation and 20-25 mm 2 between 32 and 40 weeks of gestation.
To ensure that the ROIs were representative, the relative standard deviation of all pixels needed to be < 10% of the mean ADC values.

Cephalic index of the fetal brain
In order to correct for differences in head size, cephalic index (CI) was considered by measuring the biparietal diameter (BPD) and occipitofrontal diameter (OFD) 6 . To calculate the CI, we used a previously reported formula: CI = BPD/OFD × 100. All of the length, thickness and area measurements of the CC were adjusted by CI, for group comparison purposes.

Reliability between macrostructural and microstructural measurements of the fetal CC
Reliability between measurements from W.Z. and X.Z. blinded to group membership was assessed by the intra class correlation coefficients (ICCs) (two-way random mixed for absolute agreement) and their 95% confidence intervals (eTable 1). To verify the reliability of linear and area measurement, fourteen fetuses (25%) were randomly selected for each group. To verify the reliability of ADC measurement, ten fetuses (25%) were randomly selected for each group. An ICCs of 1 indicates perfect reproducibility between measurements, while a value of 0 is interpreted as reproducibility that is no better (ICCs = 0.500-0.750), good (ICCs = 0.750-0.900), and excellent (ICCs > 0.900