Longitudinal investigation of neurobiological changes across pregnancy

Abstract

Pregnancy is a period of profound biological transformation. However, we know remarkably little about pregnancy-related brain changes. To address this gap, we chart longitudinal changes in brain structure during pregnancy and explore potential mechanisms driving these changes. Ten participants (Mean age = 28.97 years) are assessed 1-6 times (median = 3) during their pregnancy. Each visit includes anatomical and diffusion-weighted MRI, and assessments of waking salivary hormones, hair hormones, and inflammatory cytokines. Here we observe a reduction in gray matter volume and an increase in neurite density index (NDI), a proxy of axon density, in white matter tracts across pregnancy. Progesterone levels are associated with reductions in brain volumetric measurements, and both progesterone and estradiol levels are linked to increases in NDI in white matter tracts. This study highlights the profound neurobiological changes experienced by pregnant individuals and provides insights into neuroplasticity in adulthood.

Fig. 1. The observed decrease in brain volumes throughout the course of pregnancy.

The plots are based on the linear mixed-effects model shown in Eq. (1). Specifically, brain metrics were the dependent variables, and gestational week was the predictor, covarying for age and total intracranial volume. GM: gray matter, WM: white matter. The shaded area represents the 95% confidence interval (95% CI) for the fitted line. Note. **p < 0.01.

Fig. 2. Illustration of the association between cortical region volumes, as defined by the Desikan-Killiany atlas, and gestational week.

a The figure is color-coded to reflect the standardized regression coefficients derived from linear mixed-effects models, which were fitted for each cortical region volume against gestational week while covarying for age and total intracranial volume (Eq. 2). b The figure selectively presents the cortical regions that exhibited a significant volume decrease throughout pregnancy. No multiple comparison correction was implemented.

Fig. 3. Illustration of the association between Neurite Density Index (NDI) and the progression of pregnancy.

The figure is color-coded to represent the standardized regression coefficients from linear mixed-effects models fitted for NDI against gestational week while covarying for age and relative motion (Eq. 2). CST: Corticospinal Tract, FPT: Fronto-Pontine Tract, POPT: Parieto‐Occipital Pontine, SCP: Superior Cerebellar Peduncle, STR: Superior Thalamic Radiation, T_PREM: Thalamo-Premotor, ST_PREM: Striato-Premotor.

Fig. 4. The increase in total intracranial cerebrospinal fluid (CSF) was observed across pregnancy.

The plot is based on the linear mixed-effects model shown in Eq. (1). Specifically, CSF was the dependent variable and gestational week was the predictor, covarying for age and total intracranial volume. The shaded area represents the 95% confidence interval (95% CI) for the fitted line. Note. *p < .05.

Fig. 5. The observed changes in hormone levels during pregnancy and associations between progesterone levels and brain structural metrics.

a The observed changes in hormone levels (progesterone, estradiol, testosterone, and cortisol) during pregnancy. Linear mixed-effects models were applied with hormone levels as the dependent variable and gestational week as the predictor, covarying for age. b Associations between progesterone levels and brain structural metrics, including total brain volume, total gray matter volume, total cortical volume, and cortical thickness. The plot is based on Eq. 3. Specifically, brain metrics were the dependent variable and progesterone was the predictor, covarying for age and total intracranial volume. The shaded area represents the 95% confidence interval (95% CI) for the fitted line. Note. **p < .01. ***p < .001.

Fig. 6. The association between Neurite Density Index (NDI) and hormone levels (specifically progesterone, estradiol, and cortisol).

The color-coding reflects the standardized regression coefficients obtained from linear mixed effects models, which were used to analyze the relation between NDI and each of the three hormones while covarying for age and relative motion (Eq. 4). Note. *p < .05. **p < .01. ***p < .001. An asterisk in the color bar indicates the level of significance for standardized regression coefficients.

Fig. 7. Illustration of the gestational weeks range captured for participants.

Zero on the x-axis denotes the first day of the last menstrual period, with conception following approximately two weeks later.