94% of the grey matter in the brains of mothers undergoes changes during pregnancy
A study led by the UAB has analysed the brains of women during pregnancy for the first time using neuroimaging techniques. The study included non-pregnant mothers, whose partners were pregnant, to distinguish biological effects from those caused by the experience of being a mother. The research shows that there is a reduction and partial recovery of almost 5% of grey matter in 94% of the total grey matter volume of the brain, especially in regions linked to social cognition.
Researchers from the Universitat Autònoma de Barcelona (UAB), the Gregorio Marañón Health Research Institute and the Hospital del Mar Research Institute, together with other prestigious international institutions, have published the first longitudinal neuroimaging (Magnetic Resonance Imaging) study in a cohort of more than a hundred women seeking to become mothers for the first time. The findings reveal a dynamic trajectory in the brain during pregnancy and postpartum, significantly linked to the steroid hormone fluctuations inherent to pregnancy, and to the psychological well-being of the mothers. The article, led by Camila Servin-Barthet and Magdalena Martínez-García as first authors and coordinated by Òscar Vilarroya and Susana Carmona, has been recently published in the prestigious journal Nature Communications. This study, which received a grant of 972,414 euros from the ”la Caixa” Foundation to be carried out, represents a crucial advance in maternal brain research.
In total, the researchers have analyzed the brain of 179 women to study the structural changes that occur during the second and third trimester of pregnancy and the first six months postpartum, using a scan taken before conception as a baseline. For the first time, this cohort includes a group of non-gestational mothers as a control group: women whose partners underwent pregnancy during the study. The inclusion of this group of women made it possible to determine that the trajectory of brain changes is mainly attributed to the biological process of pregnancy, rather than to the experience of becoming a mother.
This work has revealed that, during the first pregnancy, gray matter volume in the brain is reduced by up to 4.9%, with a partial recovery during the postpartum period. These changes are observed in 94% of the brain, being particularly prominent in regions linked to social cognition. The study also demonstrates, for the first time, that the evolution of these morphological changes in the brain is associated with fluctuations in two estrogens (estriol-3-sulfate and estrone-sulfate), hormones that increase exponentially during pregnancy and return to basal levels after delivery. Specifically, the researchers observed that a greater increase and subsequent decrease in estrogen levels is associated with a greater decrease and subsequent recovery of brain gray matter volume.
Finally, in analyzing the possible influence of brain changes on maternal behavior, this study discovered that women with a higher percentage of gray matter volume recovery during postpartum reported a greater bond with their infant at 6 months postpartum, and that maternal well-being is a key factor that positively enhances the association between brain changes and maternal-filial bonding.
This study, which comprehensively characterizes normative brain changes during pregnancy and postpartum, stands out for both its sample size and rigorous methodological control, including carefully selected groups that allowed the distinguishing of pregnancy-specific changes from those linked to the experience of motherhood. The data obtained not only establishes a key reference for understanding the neurobiology of the maternal brain, but also serves as a basis for future studies analyzing other neuroimaging modalities and more diverse samples, including women with clinical conditions such as postpartum depression, allowing progress towards a more complete and applied understanding of the brain in this vital period.
Journal
Nature Communications
Method of Research
Observational study
Subject of Research
People
Article Title
Pregnancy entails a U-shaped trajectory in human brain structure linked to hormones and maternal attachment
Pregnancy triggers profound brain changes, enhancing maternal instincts and mental health
Scientists uncover how pregnancy transforms the brain, with gray matter changes that shape maternal instincts and well-being for the long haul.
Study: Pregnancy entails a U-shaped trajectory in human brain structure linked to hormones and maternal attachment. Image Credit: Maridav / Shutterstock
In a recent study published in the journal Nature Communications, researchers conducted a longitudinal study to investigate the neurological changes accompanying human pregnancy, particularly for first-time mothers.
Their study spanned pre-pregnancy, during pregnancy, and postpartum and discovered that gray matter (GM) volume evolves in a U-shaped pattern—it first declines during late pregnancy and then recovers in the six months postpartum. The study found that GM volume declined by 2.7% during the second trimester and 4.9% immediately before delivery, followed by a 3.4% recovery postpartum. Hormonal evaluations suggest that these changes are caused by pregnancy-associated estrogen fluctuations, with estriol sulfate and estrone sulfate identified as key factors rather than parenting experience.
Notably, maternal mental health was found to influence the relationship between postpartum GM recovery (volume) and maternal attachment. Specifically, maternal well-being mediated over 50% of the relationship between GM volume recovery and maternal attachment, highlighting its critical role. These findings provide the first evidence for the previously hypothesized U-shaped GM pattern, filling a significant neuroscience knowledge gap and forming the basis for future neuroimaging investigations to improve maternal mental health and well-being.
Background
Pregnancy is arguably the most transformative period in a female’s life, particularly in animals exhibiting parental care. Globally, more than 140 million females give birth yearly, with previous neuroimaging research identifying significant brain architecture remodeling accompanying the process. These studies suggest that brain remodeling helps equip pregnant women for motherhood by enhancing their maternal attachment.
Concurrent studies in murine (rodent) model systems have identified steroid hormone alterations that may facilitate maternal behaviors. A recent observation-driven hypothesis posits that human brains may undergo cortical gray matter (GM) volume evolution during pregnancy and that this volume change may follow a U-shaped pattern of initial loss (during pregnancy) and subsequent gain (postpartum). Unfortunately, this hypothesis or the factors influencing its manifestation (such as hormones, maternal experience, and mental health) have never been tested.
About the study
The present prospective study aims to address these knowledge gaps using cutting-edge Magnetic Resonance Imaging (MRI), neuropsychological assessments, and hormone analyses across the temporal pregnancy spectrum (before, during, and following pregnancy and birth). To ensure that the patterns observed were restricted to the maternal process, data from prospective mothers (termed ‘gestational mothers’; n = 127) were compared to nulliparous women (those with no pregnancy plans throughout the study; n = 32).
Furthermore, to unravel the role of physiological changes versus the parenting experience, data from gestational mothers were compared with those from ‘non-gestational mothers (n = 20),’ partners of gestational mothers who shared the parenting experience (baby upkeep) without being pregnant.
The study was carried out over five sessions – before conception, second trimester, third trimester, one month postpartum, and six months postpartum. Each session comprised a comprehensive MRI evaluation, urine sample collection (for hormone/endocrine assessments), and mental health questionnaires. The MRIs were optimized to scan and image global cortical GM volume, surface area, and thickness, providing a comprehensive assessment of brain changes.
MRI data in tandem with urine-derived steroid metabolite quantification was used to unravel the associations between brain structural evolution and gestational hormones. Among 49 hormones analyzed, only estriol sulfate and estrone sulfate showed significant negative correlations with GM volume changes, suggesting their role in triggering or modulating outcomes of interest. Finally, questionnaire data and mental health records were used to assess the parental experience and psychological well-being contributions to observed neurological evolution.
Study findings
This study is the first to confirm the increasingly popular hypothesis that GM volume evolves in a U-shaped pattern over the duration of pregnancy. GM volume declines during the second trimester (by 2.7%) and immediately before gestation (by 4.9%). These changes were symmetric across both brain hemispheres, with the most significant declines in the Default Mode and Frontoparietal brain regions.
GM volume recovered by 3.4% at six months postpartum but did not fully return to pre-pregnancy levels, suggesting possible long-term adaptations. While more extended follow-up periods are required to confirm this hypothesis, current study data suggest that GM volume changes during a woman’s first pregnancy may have lifelong effects, permanently equipping her for motherhood via enhanced maternal attachment. GM volumes remained unaltered in nulliparous and non-gestational cohorts.
Linked evolution analyses between neuroanatomical observations (MRI scans) and hormone quantification (analyzing 49 hormones) revealed that only two hormones, estriol sulfate, and estrone sulfate, were negatively correlated with GM volume in a temporally mirrored fashion, suggesting the role of sulfated estrogens in triggering or modulating outcomes of interest.
Finally, evaluations of the interplay between brain structural changes, maternal mental health (maternal well-being, postnatal depression, and perceived stress), and baby attachment revealed interesting results –
- Greater GM recovery postpartum was positively associated with reduced hostility toward the baby,
- Maternal well-being directly increased the extent of GM recovery postpartum (and, in turn, affected the first result), and
- Postnatal depression and perceived stress were not significantly associated with changes in maternal affection or GM volume.
Conclusion
The present study is the first to validate that women undergo substantial GM volume changes throughout their pregnancy, observed as a U-shaped pattern of initial pre-delivery loss and subsequent postpartum gain. Estrogens, specifically estriol sulfate and estrone sulfate, are likely the driver of these changes, with the parenting experience playing little to no role in brain structural modifications. Additionally, functional connectivity analyses revealed no significant changes in network modularity, segregation, or participation coefficient across the pregnancy period.
Maternal well-being was found to be the strongest determinant of postpartum GM recovery and, in turn, maternal attachment, mediating over half of the observed effect.
- Servin-Barthet, C., Martínez-García, M., Paternina-Die, M. et al. Pregnancy entails a U-shaped trajectory in the human brain structure linked to hormones and maternal attachment. Nat Commun 16, 730 (2025), DOI – 10.1038/s41467-025-55830-0, https://www.nature.com/articles/s41467-025-55830-0
