Pediatr Res. 2026 Jan 15. doi: 10.1038/s41390-025-04726-2. Online ahead of print.

ABSTRACT

BACKGROUND: Elevated pre-pregnancy body mass index (BMI) and perinatal depressive symptoms have been linked to neonatal alterations in brain structure and function. This study examined associations between neonatal functional brain dynamics, maternal BMI, and perinatal depressive symptoms measured by the Edinburgh Postnatal Depression Scale (EPDS) in a community-based, largely low-risk cohort.

METHODS: Funcitonal MRI and Leading Eigenvector Analysis (LEiDA) were applied in a neonatal cohort (N = 437; 236 males; mean gestational age 39.6 weeks) from the developing Human Connectome Project. We assessed whether neonatal brain-state probabilities related to maternal BMI and EPDS scores (M = 5.6, SD = 4.3), testing main effects and, separately, their interaction. The sample included 291 healthy-weight (BMI < 25), 98 overweight (25 BMI < 30), and 48 obese (BMI 30) mothers.

RESULTS: EPDS scores were low in this cohort and did not demonstrate associations with brain states or a significant BMI × EPDS interaction. Higher maternal pre-pregnancy BMI was negatively associated with the stability of a functional network encompassing superior frontal, superior parietal, and temporal regions (ß = -0.129, p = 0.006).

CONCLUSION: As this network is normally recruited more with age, reduced stability suggests slowed maturation of fronto-parieto-temporal systems and may signal early risk for later behavioral challenges.

IMPACT: Higher maternal pre-pregnancy BMI is associated with reduced stability in a neonatal frontoparietal brain state, characterized by coordinated activity in frontal, parietal, and temporal regions. This state is one of six distinct dynamic connectivity patterns identified, reflecting core neonatal resting-state networks. The association was robust across multiple analytic models and clustering solutions. No significant effects were found for maternal depressive symptoms. These findings underscore the selective impact of maternal metabolic health on early brain organization, suggesting prenatal influences on the functional architecture of the newborn brain that may shape long-term neurodevelopmental trajectories.

PMID:41540202 | DOI:10.1038/s41390-025-04726-2