In this study we explored whether maternal pre-pregnancy BMI affects neonate brain local functional connectivity. Multiple regression analysis revealed that maternal pre-pregnancy BMI and neonate ReHo values were positively associated (FDR/FWE –corrected p < 0.005, cluster size of 869 voxels) within the left SFG, suggesting that higher maternal BMI during pre-pregnancy or early pregnancy influences neonatal local brain connectivity.
In neonates soon after birth, high ReHo values are encountered symmetrically in primary somatosensory and visual networks (mean ReHo map shown in Supplementary materials, Figs. 1 and 39). Notably, previous developmental fMRI connectivity studies have estimated that these networks achieve adult-like network topology and function earlier than e.g. frontoparietal, executive control and default-mode networks 16,18,19. In line with this idea, prior modelling studies have suggested an inverse relationship between distal connectivity and ReHo regarding a given voxel 38, suggesting that as functional segregation of networks ensues, ReHo values decrease. In this framework, our observation that ReHo in the left SFG was higher in neonates born to mothers with higher BMIs likely relates to amplified local, and conversely, decreased distal connectivity in this region.
The left SFG has been identified as a key hub in the left frontoparietal network (FPN), which holds a central role in executive control, working memory and fluid intelligence in adults 40. Furthermore, SFGs have been recognized as crucial areas for global networks in terms of network centrality in adults 41 and identified as a possible connector hub between executive control network and default-mode-network 42. However, in their immature state, brain networks in neonates likely have divergent functions as compared to corresponding networks in older infants and adults, complicating network-related change interpretation and comparison between populations of different age. For the left FPN, increase in within-network and in inter-network connectivity between lateral visual, auditory/language and right FP networks with simultaneous decreases in inter-network connectivity between medial visual and salience networks take place during the first year of life 18. In light of previous studies into functional resting-state-network development and ReHo interpretation, the observed positive association between maternal pre-pregnancy BMI and neonate left SFG ReHo values in this study may suggest accelerated within-network development. Whether this is reflected as altered inter-network connectivity regarding lateral visual, auditory/language and right FP or other networks, remains unclear. If inter-network and distal connectivity are altered, it might explain some of the observed cognitive performance differences seen in older children born from obese and overweight pregnancies 2,3.
Prior investigations into maternal obesity and overweight during pregnancy related infant neurodevelopment have revealed widespread functional connectivity and white matter tract alterations in the neonate brain 22–25. Similarly, a recent study found that higher pre-pregnancy maternal BMI during gestation associated with variations in functional connectivity in fetal prefrontal, frontal and insular brain regions 43. These results suggest that at least some group differences observed in obese/overweight and normal-weight populations could begin during the gestational period and may be attributed to metabolic, humoral and inflammatory processes in obese mothers. Indeed, obesity/overweight related changes in brain network organization have been well documented in adult populations with alterations emphasizing to four distinct domains concerned with feeding behavior: Sensory cue processing 44, reward processing 45, cognitive 44 and motor control 46. A recent seed-based connectivity study hypothesized that these network abnormalities could be inherited through genetic or environmental effects and observed similar functional connectivity differences in neonates exposed to maternal obesity during gestation 25. To the best of our knowledge, no structural MRI studies have been performed on neonates born from pregnancies with maternal obesity, but studies focusing on older obese/overweight children have found grey matter abnormalities within the frontal, prefrontal and limbic areas 47. Moreover, the observed GM reduction were partly associated with impaired executive function 47. These abnormalities mainly spatially overlap with functional changes seen in neonates born from pregnancies with maternal obesity/overweight and likely precede structural abnormalities seen in older children and may begin as early as gestation.
Despite the observable widespread connectivity differences between neonates born from normal-weight and pregnancies with maternal obesity, it is unclear whether these changes are driven by systemic effects of insults or caused by localized impairment of key regions, e.g. connector hubs, followed by plasticity induced changes within plural functional networks, causing global differences in connectivity. It is likely that divergent detrimental factors have a heavier impact on specific regions and those most vulnerable are presumably areas crucial for networks that take years to reach maturity and obtain coherent function 13.