Maternal pre-pregnancy obesity affects the uncinate fasciculus white matter tract in preterm infants

Abstract

Background: A growing body of evidence suggests an association between a higher maternal pre-pregnancy body mass index (BMI) and adverse long-term neurodevelopmental outcomes for their offspring. Despite recent attention to the effects of maternal obesity on fetal and neonatal brain development, changes in the brain microstructure of preterm infants born to mothers with pre-pregnancy obesity are still not well understood. This study aimed to detect the changes in the brain microstructure of obese mothers in pre-pregnancy and their offspring born as preterm infants using diffusion tensor imaging (DTI).

Methods: A total of 32 preterm infants (born to 16 mothers with normal BMI and 16 mothers with a high BMI) at <32 weeks of gestation without brain injury underwent brain magnetic resonance imaging at term-equivalent age (TEA). The BMI of all pregnant women was measured within approximately 12 weeks before pregnancy or the first 2 weeks of gestation. We analyzed the brain volume using a morphologically adaptive neonatal tissue segmentation toolbox and calculated the major white matter (WM) tracts using probabilistic maps of the Johns Hopkins University neonatal atlas. We investigated the differences in brain volume and WM microstructure between preterm infants of mothers with normal and high BMI. The DTI parameters were compared among groups using analysis of covariance adjusted for postmenstrual age at scan and multiple comparisons.

Results: Preterm infants born to mothers with a high BMI showed significantly increased cortical gray matter volume (p = 0.001) and decreased WM volume (p = 0.003) after controlling for postmenstrual age and multiple comparisons. We found a significantly lower axial diffusivity in the uncinate fasciculus (UNC) in mothers with high BMI than that in mothers with normal BMI (1.690 ± 0.066 vs. 1.762 ± 0.101, respectively; p = 0.005).

Conclusion: Our study is the first to demonstrate that maternal obesity impacts perinatal brain development patterns in preterm infants at TEA, even in the absence of apparent brain injury. These findings provide evidence for the detrimental effects of maternal obesity on brain developmental trajectories in offspring and suggest potential neurodevelopmental outcomes based on an altered UNC WM microstructure, which is known to be critical for language and social-emotional functions.

Keywords: diffusion tensor imaging; maternal obesity; obesity; pre-pregnancy; preterm birth; uncinate fasciculus; white matter.