Brain Development in Fetuses of Mothers with Diabetes: A Case-Control MR Imaging Study.

BACKGROUND AND PURPOSE: Offspring exposed to maternal diabetes are at increased risk of neurocognitive impairment, but its origins are unknown. With MR imaging, we investigated the feasibility of comprehensive assessment of brain metabolism (1H-MRS), microstructure (DWI), and macrostructure (structural MRI) in third-trimester fetuses in women with diabetes and determined normal ranges for the MR imaging parameters measured. MATERIALS AND METHODS: Women with singleton pregnancies with diabetes (n = 26) and healthy controls (n = 26) were recruited prospectively for MR imaging studies between 34 and 38 weeks' gestation. RESULTS: Data suitable for postprocessing were obtained from 79%, 71%, and 46% of women for 1H-MRS, DWI, and structural MRI, respectively. There was no difference in the NAA/Cho and NAA/Cr ratios (mean [SD]) in the fetal brain in women with diabetes compared with controls (1.74 [0.79] versus 1.79 [0.64], P = .81; and 0.78 [0.28] versus 0.94 [0.36], P = .12, respectively), but the Cho/Cr ratio was marginally lower (0.46 [0.11] versus 0.53 [0.10], P = .04). There was no difference in mean [SD] anterior white, posterior white, and deep gray matter ADC between patients and controls (1.16 [0.12] versus 1.16 [0.08], P = .96; 1.54 [0.16] versus 1.59 [0.20], P = .56; and 1.49 [0.23] versus 1.52 [0.23], P = .89, respectively) or volume of the cerebrum (243.0 mL [22.7 mL] versus 253.8 mL [31.6 mL], P = .38). CONCLUSIONS: Acquiring multimodal MR imaging of the fetal brain at 3T from pregnant women with diabetes is feasible. Further study of fetal brain metabolism in maternal diabetes is warranted.

Epigenomic profiling of preterm infants reveals DNA methylation differences at sites associated with neural function.

DNA methylation (DNAm) plays a determining role in neural cell fate and provides a molecular link between early-life stress and neuropsychiatric disease. Preterm birth is a profound environmental stressor that is closely associated with alterations in connectivity of neural systems and long-term neuropsychiatric impairment. The aims of this study were to examine the relationship between preterm birth and DNAm, and to investigate factors that contribute to variance in DNAm. DNA was collected from preterm infants (birth<33 weeks gestation) and healthy controls (birth>37 weeks), and a genome-wide analysis of DNAm was performed; diffusion magnetic resonance imaging (dMRI) data were acquired from the preterm group. The major fasciculi were segmented, and fractional anisotropy, mean diffusivity and tract shape were calculated. Principal components (PC) analysis was used to investigate the contribution of MRI features and clinical variables to variance in DNAm. Differential methylation was found within 25 gene bodies and 58 promoters of protein-coding genes in preterm infants compared with controls; 10 of these have neural functions. Differences detected in the array were validated with pyrosequencing. Ninety-five percent of the variance in DNAm in preterm infants was explained by 23 PCs; corticospinal tract shape associated with 6th PC, and gender and early nutritional exposure associated with the 7th PC. Preterm birth is associated with alterations in the methylome at sites that influence neural development and function. Differential methylation analysis has identified several promising candidate genes for understanding the genetic/epigenetic basis of preterm brain injury.

Measurement of fetal fat in utero in normal and diabetic pregnancies using magnetic resonance imaging.

OBJECTIVES: To assess the reliability of magnetic resonance imaging (MRI) to measure fetal fat volume in utero, and to study fetal growth in women with and without diabetes in view of the increased prevalence of macrosomia in the former. METHODS: We studied 26 pregnant women, 14 with pre-gestational diabetes and 12 non-diabetic controls. Fetal assessment took place at 24 weeks' gestation and again at 34 weeks by standard ultrasound biometry followed by MRI at 1.5 T. Fetal fat volume was determined from T1-weighted water-suppressed images using a semi-automated approach based on pixel intensity and taking into account partial volume effects. Fetal volume was also determined from the MRI images. Fetal weight was calculated using published fat and lean tissue densities. RESULTS: There was little fetal fat at 24 weeks' gestation, but at 34 weeks the fetal fat content was considerably higher in the women with diabetes, with a mean fat content of 1090 ± 417 cm(3) compared with 541 ± 348 cm(3) in the controls (P = 0.006). Measurements of fetal fat volume showed low intra- and interobserver variability at 34 weeks, with intraclass correlation coefficients consistently above 0.99. Birth-weight centile correlated with fetal fat volume (R(2) = 0.496, P < 0.001), percentage of fetal fat (R(2) = 0.362, P = 0.008) and calculated fetal weight (R(2) = 0.492, P < 0.001) at 34 weeks. CONCLUSIONS: MRI appears to be a promising tool for the determination of fetal fat, body composition and weight in utero during the third trimester of pregnancy.