Long-term association of pregnancy and maternal brain structure: the Rotterdam Study

Abstract

The peripartum period is the highest risk interval for the onset or exacerbation of psychiatric illness in women’s lives. Notably, pregnancy and childbirth have been associated with short-term structural and functional changes in the maternal human brain. Yet the long-term effects of pregnancy on maternal brain structure remain unknown. We investigated a large population-based cohort to examine the association between parity and brain structure. In total, 2,835 women (mean age 65.2 years; all free from dementia, stroke, and cortical brain infarcts) from the Rotterdam Study underwent magnetic resonance imaging (1.5 T) between 2005 and 2015. Associations of parity with global and lobar brain tissue volumes, white matter microstructure, and markers of vascular brain disease were examined using regression models. We found that parity was associated with a larger global gray matter volume (β = 0.14, 95% CI = 0.09–0.19), a finding that persisted following adjustment for sociodemographic factors. A non-significant dose-dependent relationship was observed between a higher number of childbirths and larger gray matter volume. The gray matter volume association with parity was globally proportional across lobes. No associations were found regarding white matter volume or integrity, nor with markers of cerebral small vessel disease. The current findings suggest that pregnancy and childbirth are associated with robust long-term changes in brain structure involving a larger global gray matter volume that persists for decades. Future studies are warranted to further investigate the mechanism and physiological relevance of these differences in brain morphology.

Protective role of parenthood on age-related brain function in mid- to late-life

“…Here, we discuss the potential for these effects to be driven by a combination of 1) direct/caregiving, 2) indirect/environmental, and/or 3) covarying/sociodemographic mechanisms. While the factors underpinning this neuroprotective effect require further study, these results are consistent with the extant human and animal parental brain literatures, which point to structural [27][28][29][30][31][32][33] and functional 26 neuroprotection in mothers [26][27][28][29][30][31][32][33] and fathers 30 with more children.…”

“…This effect is strong at an individual connection-level, and even stronger at a network-level, and exists for both females and males, suggesting a neuroprotective effect of parenthood on brain function in later life. This finding, though striking, is in line with our hypothesis, as well as the current understanding of the enduring impact of parenthood on the parental brain in humans [27][28][29][30][31][32] and animals [34][35][36] . Indeed, a growing literature examining brain structure in later life parenthood demonstrates 'younger-looking' brains in adults with more children [27][28][29][30][31][32][33] , painting a consistent picture of parity-related protection for the structure of the adult brain.…”

“…Critically, we find that for both females and males, patterns of parenthood-related brain function are in the opposite direction to those associated with aging, which showed lower functional connectivity across the somato/motor network and higher connectivity within cortico-subcortical systems with age. Our findings closely align with past human [26][27][28][29][30][31][32][33] and animal [34][35][36][37] work suggesting long-term neuroprotection related to parenthood throughout the lifespan.…”

“…Recent large-scale population neuroscience studies have demonstrated a consistent picture of the long-term structural brain adaptations related to parenthood. These studies show an association between the number of children a person has parented (parity) and 'younger-looking' brain structure [27][28][29][30][31][32][33] and function 26 , in line with earlier work in rodents [34][35][36] and non-human primates 37 , suggesting a potentially neuroprotective effect of parity on the human maternal brain, worthy of further study.…”

Association of Cumulative Lifetime Exposure to Female Hormones With Cerebral Small Vessel Disease in Postmenopausal Women in the UK Biobank

“…30 This is in line with previous studies showing that parity and longer reproductive lifespans are associated with lower rates of silent brain infarcts, 31 strokes, 32 dementia, 33 and brain atrophy. [34][35][36][37] Alternatively, studies have suggested that the rather subtle increase in WMHV associated with normal aging 38 is linked to microglial and endothelial activation, 28,39 indicating that women with high premenopausal LHE may be better protected against age-related inflammation of the brain. 40 This agrees with animal models showing that circulating estrogen can reduce the inflammatory response, which could be dose-dependent.…”