was nearly three times higher than controls scanned over a similar 
duration (Supplementary Fig. 11a,b). This extends to MTL subfields, 
wherein change in volume was three to four times greater across gesta-
tion than normative brain variability (Supplementary Fig. 11c,d). We 
contextualized these findings further by comparing gestational GMV 
change against our participant’s preconception brain volumes; average 
GMV change during pregnancy was six times (cortical) and three times 
(MTL) higher than the variability observed between baseline sessions.
subcortical structures, including the ventral diencephalon, caudate, 
thalamus, putamen and hippocampus. High-resolution imaging and 
segmentation of the medial temporal lobe (MTL) extend these findings 
further, revealing specific volumetric reductions within hippocampal 
subfields CA1, CA2/CA3 and parahippocampal cortex (PHC). In con -
trast to widespread decreases in cortical and subcortical GMV, cor -
relational tractography analyses revealed nonlinear increases in white 
matter quantitative anisotropy (QA) throughout the brain—indicating 
greater tract integrity—as gestational week progressed. T ogether, these 
findings reveal the highly dynamic changes that unfold in a human 
brain across pregnancy, demonstrating a capacity for extensive neural 
remodeling well into adulthood.
Results
Serological evaluations
Serological evaluations captured canonical hormone fluctuations 
characteristic of the prenatal, perinatal and postnatal periods (Fig. 1b). 
Serum hormone concentrations increased significantly over the course 
of pregnancy and dropped precipitously postpartum (preconcep -
tion, estradiol (E) = 3.42 pg ml−1 and progesterone (P) = 0.84 ng ml−1;  
3 weeks preparturition, E = 12,400 pg ml−1 and P = 103 ng ml−1; 3 months 
postparturition, E = 11.50 pg ml−1 and P = 0.04 ng ml−1).
Whole-brain dynamics from baseline through postpartum
T o begin, we characterized broad neuroanatomical changes over the 
course of the entire experimental window (baseline—2 years postpar-
tum, 26 scans; Fig. 1d). Generalized additive models revealed strong 
nonlinear (effective degrees of freedom > 3) relationships between 
weeks since conception and summary brain metrics. T otal GMV 
(F = 27.87, P < 0.001, deviance explained = 93.9%, R2
adj = 0.91), summary 
CT (F = 15.79, P < 0.001, deviance explained = 78.6%, R2
adj = 0.75) and 
total brain volume (F = 26.12, P < 0.001, deviance explained = 93.4%, 
R2
adj = 0.90) linearly decreased during gestation and appeared to 
partially rebound postpartum. In contrast, global microstructural 
integrity (QA) of white matter increased throughout the first and sec-
ond trimesters before returning to baseline levels in the postpartum 
period (whole-brain QA, F = 4.62, P = 0.007, deviance explained = 60.2%, 
R2
adj = 0.51). We also observed nonlinear patterns of lateral ventricle 
expansion (F = 10.44, P < 0.001, deviance explained = 83.8%, R2
adj = 0.77) 
and increased cerebrospinal fluid (CSF; F = 13.32, P < 0.001, deviance 
explained = 83.8%, R2
adj = 0.79) rising in the second and third trimesters 
before dropping sharply postpartum.
Cortical volume and thickness changes tied to gestation
We then narrowed the aperture to capture changes unfolding within 
gestation itself (baseline—36 weeks pregnant, 19 scans). Relationships 
between summary brain metrics were evident over the gestational 
period as follows: total brain volume, GMV and CT were positively asso-
ciated with one another, whereas lateral ventricles, CSF and global QA 
demonstrated negative relationships with GMV (Supplementary Fig. 1).
Changes in GMV were near-ubiquitous across the cortical mantle 
(Fig. 2a). Most large-scale brain networks exhibited decreases in GMV 
(Fig. 2b and Supplementary Table 1); indeed, 80% of the 400 regions of 
interest (ROI) demonstrated negative relationships between GMV and 
gestation week (Fig. 2a and Supplementary Table 2). T ogether, these