Maternal pre-pregnancy BMI associates with neonate local and distal functional connectivity of the left superior frontal gyrus

Olli Rajasilta,Riitta Parkkola,Satu J Lehtola,Tuire Lähdesmäki,Jani Saunavaara,Jetro J Tuulari,Noora M Scheinin,Suvi Häkkinen,Malin Björnsdotter,Linnea Karlsson,Hasse Karlsson

doi:10.1038/s41598-021-98574-9

Abstract

Maternal obesity/overweight during pregnancy has reached epidemic proportions and has been linked with adverse outcomes for the offspring, including cognitive impairment and increased risk for neuropsychiatric disorders. Prior neuroimaging investigations have reported widespread aberrant functional connectivity and white matter tract abnormalities in neonates born to obese mothers. Here we explored whether maternal pre-pregnancy adiposity is associated with alterations in local neuronal synchrony and distal connectivity in the neonate brain. 21 healthy mother-neonate dyads from uncomplicated pregnancies were included in this study (age at scanning 26.14 ± 6.28 days, 12 male). The neonates were scanned with a 6-min resting-state functional magnetic resonance imaging (rs-fMRI) during natural sleep. Regional homogeneity (ReHo) maps were computed from obtained rs-fMRI data. Multiple regression analysis was performed to assess the association of pre-pregnancy maternal body-mass-index (BMI) and ReHo. Seed-based connectivity analysis with multiple regression was subsequently performed with seed-ROI derived from ReHo analysis. Maternal adiposity measured by pre-pregnancy BMI was positively associated with neonate ReHo values within the left superior frontal gyrus (SFG) (FWE-corrected p < 0.005). Additionally, we found both positive and negative associations (p < 0.05, FWE-corrected) for maternal pre-pregnancy BMI and seed-based connectivity between left SFG and prefrontal, amygdalae, basal ganglia and insular regions. Our results imply that maternal pre-pregnancy BMI associates with local and distal functional connectivity within the neonate left superior frontal gyrus. These findings add to the evidence that increased maternal pre-pregnancy BMI has a programming influence on the developing neonate brain functional networks.

Highlights

Maternal obesity (BMI ≥ 30 kg/m2) and overweight (BMI ≥ 25–30 kg/m2) during pregnancy have become prevalent worldwide within the last few d ecades[1]
Including maternal age as an additional independent variables (IV) to the original model reduced the original effect to statistical insignificance at p < 0.05 level
In this study we explored whether maternal pre-pregnancy BMI affects neonate brain local and distal functional connectivity

Summary

Introduction

Maternal obesity (BMI ≥ 30 kg/m2) and overweight (BMI ≥ 25–30 kg/m2) during pregnancy have become prevalent worldwide within the last few d ecades[1]. Animal model investigations into maternal obesity and offspring brain development have provided some insight on the mechanisms, including dysregulation within serotonergic and dopaminergic systems[9,10], altered hypothalamic–pituitary–adrenal axis (HPA-axis) r esponses[11], fetal neuronal d amage[12] and changes in offspring brain gene expression p atterns[12]. Prior human MRI neonate studies focusing on obese and overweight pregnancies have revealed that maternal adiposity is associated with widespread alterations in the anterior brain white matter tract integrity[25] and in functional networks[26,27] with emphasis on sensory cue and reward processing, cognitive and motor control in the neonate b rain[28]. We implemented seed-based connectivity analysis (SCA) to investigate whether alterations in ReHo are reflected in distal functional connectivity

Results

Discussion

Conclusion