Maternal Obesity during Pregnancy is Associated with Lower Cortical Thickness in the Neonate Brain.

BACKGROUND AND PURPOSE: Recent studies have suggested that maternal obesity during pregnancy is associated with differences in neurodevelopmental outcomes in children. In this study, we aimed to investigate the relationships between maternal obesity during pregnancy and neonatal brain cortical development. MATERIALS AND METHODS: Forty-four healthy women (28 normal-weight, 16 obese) were prospectively recruited at <10 weeks' gestation, and their healthy full-term neonates (23 boys, 21 girls) underwent brain MR imaging. All pregnant women had their body composition (fat mass percentage) measured at ∼12 weeks of pregnancy. All neonates were scanned at ∼2 weeks of age during natural sleep without sedation, and their 3D T1-weighted images were postprocessed by the new iBEAT2.0 software. Brain MR imaging segmentation and cortical surface reconstruction and parcellation were completed using age-appropriate templates. Mean cortical thickness for 34 regions in each brain hemisphere defined by the UNC Neonatal Cortical Surface Atlas was measured, compared between groups, and correlated with maternal body fat mass percentage, controlled for neonate sex and race, postmenstrual age at MR imaging, maternal age at pregnancy, and the maternal intelligence quotient and education. RESULTS: Neonates born to obese mothers showed significantly lower (P ≤ .05, false discovery rate-corrected) cortical thickness in the left pars opercularis gyrus, left pars triangularis gyrus, and left rostral middle frontal gyrus. Mean cortical thickness in these frontal lobe regions negatively correlated (R = -0.34, P = .04; R = -0.50, P = .001; and R = -0.42, P = .01; respectively) with the maternal body fat mass percentage measured at early pregnancy. CONCLUSIONS: Maternal obesity during pregnancy is associated with lower neonate brain cortical thickness in several frontal lobe regions important for language and executive functions.

Maternal Anxiety and Depression during Late Pregnancy and Newborn Brain White Matter Development.

BACKGROUND AND PURPOSE: Anxiety and depression during pregnancy have been associated with an increased risk of adverse neurodevelopmental outcomes in offspring. We aimed to study the in utero effects of maternal anxiety and depression on early brain development. MATERIALS AND METHODS: Pregnant women were recruited at ∼36 weeks of gestation for this prospective study. They were assessed for anxiety symptoms by the State-Trait Anxiety Inventory and for depression symptoms by the Beck Depression Inventory, 2nd Edition. After delivery, infant underwent an MR imaging examination of the brain without sedation, including DTI, for evaluation of white matter (WM) development. Infant fractional anisotropy values, a putative marker of WM integrity, were correlated with the mothers' State-Trait Anxiety Inventory and Beck Depression Inventory scores by using both tract-based spatial statistics and ROI methods. RESULTS: Thirty-four infants were included in this study. Both maternal State-Anxiety and Trait-Anxiety scores negatively correlated (P < .05, corrected) with fractional anisotropy values in widespread brain WM regions; Beck Depression Inventory scores also negatively correlated (P < .05) with fractional anisotropy values in one cluster in the brain. Further ROI analyses confirmed significant negative correlations between average fractional anisotropy values in ROIs including left and right prefrontal WM, left and right middle frontal gyrus WM, and the fornix, and State-Anxiety (R values, -0.47 to -0.67; P values, .008 to <.001), Trait-Anxiety (R, -0.37 to -0.59; P, .04 to <.001), and Beck Depression Inventory (R values, -0.36 to -0.55; P, .05 to .002) scores. CONCLUSIONS: Higher maternal anxiety and depression symptom scores during late pregnancy were associated with lower estimated infant brain WM development, which indicated in utero influences of maternal mental health during pregnancy on the developing brain.

Cesarean Delivery Impacts Infant Brain Development.

BACKGROUND AND PURPOSE: The cesarean delivery rate has increased globally in the past few decades. Neurodevelopmental outcomes associated with cesarean delivery are still unclear. This study investigated whether cesarean delivery has any effect on the brain development of offspring. MATERIALS AND METHODS: A total of 306 healthy children were studied retrospectively. We included 3 cohorts: 2-week-old neonates (cohort 1, n = 32/11 for vaginal delivery/cesarean delivery) and 8-year-old children (cohort 2, n = 37/23 for vaginal delivery/cesarean delivery) studied at Arkansas Children's Hospital, and a longitudinal cohort of 3-month to 5-year-old children (cohort 3, n = 164/39 for vaginal delivery/cesarean delivery) studied independently at Brown University. Diffusion tensor imaging, myelin water fraction imaging, voxel-based morphometry, and/or resting-state fMRI data were analyzed to evaluate white matter integrity, myelination, gray matter volume, and/or functional connectivity, respectively. RESULTS: While not all MR imaging techniques were shared across the institutions/cohorts, post hoc analyses showed similar results of potential effects of cesarean delivery. The cesarean delivery group in cohort 1 showed significantly lower white matter development in widespread brain regions and significantly lower functional connectivity in the brain default mode network, controlled for a number of potential confounders. No group differences were found in cohort 2 in white matter integrity or gray matter volume. Cohort 3 had significantly different trajectories of white matter myelination between groups, with those born by cesarean delivery having reduced myelin in infancy but normalizing with age. CONCLUSIONS: Cesarean delivery may influence infant brain development. The impact may be transient because similar effects were not observed in older children. Further prospective and longitudinal studies may be needed to confirm these novel findings.

Gestational Age at Birth and Brain White Matter Development in Term-Born Infants and Children.

BACKGROUND AND PURPOSE: Studies on infants and children born preterm have shown that adequate gestational length is critical for brain white matter development. Less is known regarding how variations in gestational age at birth in term infants and children affect white matter development, which was evaluated in this study. MATERIALS AND METHODS: Using DTI tract-based spatial statistics methods, we evaluated white matter microstructures in 2 groups of term-born (≥37 weeks of gestation) healthy subjects: 2-week-old infants (n = 44) and 8-year-old children (n = 63). DTI parameters including fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity were calculated by voxelwise and ROI methods and were correlated with gestational age at birth, with potential confounding factors such as postnatal age and sex controlled. RESULTS: Fractional anisotropy values, which are markers for white matter microstructural integrity, positively correlated (P < .05, corrected) with gestational age at birth in most major white matter tracts/regions for the term infants. Mean diffusivity values, which are measures of water diffusivities in the brain, and axial and radial diffusivity values, which are markers for axonal growth and myelination, respectively, negatively correlated (P < .05, corrected) with gestational age at birth in all major white matter tracts/regions excluding the body and splenium of the corpus callosum for the term infants. No significant correlations with gestational age were observed for any tracts/regions for the term-born 8-year-old children. CONCLUSIONS: Our results indicate that longer gestation during the normal term period is associated with significantly greater infant white matter development (as reflected by higher fractional anisotropy and lower mean diffusivity, axial diffusivity, and radial diffusivity values); however, similar associations were not observable in later childhood.

Continuous long-term culture of human bone marrow.

Human bone marrow was cultured with alpha medium, 10(-6)M hydrocortisone and a mixture of horse and fetal calf serum in a long-term liquid culture system. An adherent layer was formed with contained fat cells, macrophages, fibroblast-like and epithelioid cells. The layer harboured myeloid cells and their presumptive precursors whilst the nonadherent cells were composed of immature myeloid elements plus mature macrophages and granulocytes whose numbers were maintained for periods of up to 12 weeks. Experiments showed that the use of serum mixtures was superior to horse or fetal calf serum alone and successful culture was accompanied by early growth of the hydrocortisone-dependent fat cells in the adherent layer.