Association of Prenatal Maternal Anxiety With Fetal Regional Brain Connectivity
Open accessAbstract
Importance: Maternal psychological distress during pregnancy is associated with adverse obstetric outcomes and neuropsychiatric deficits in children. Currently unavailable in vivo interrogation of fetal brain function could provide critical insights into the onset and timing of altered neurodevelopmental trajectories. Objective: To investigate the association between prenatal maternal stress, anxiety, and depression and in vivo fetal brain resting state functional connectivity. Design, Setting, and Participants: This cohort study included pregnant women scanned between January 2016 and April 2019. A total of 50 pregnant women with healthy pregnancies were prospectively recruited from low-risk obstetric clinics in the Washington DC area and were scanned at Children's National in Washington DC. Exposures: Maternal stress, anxiety, and depression. Main Outcomes and Measures: The association of prenatal maternal stress, anxiety, and depression with whole-brain connectivity was analyzed using multivariate distance matrix regression. Prenatal maternal stress, anxiety, and depression were assessed using the Perceived Stress Scale, Spielberger State Anxiety Inventory and Spielberger Trait Anxiety Inventory, and the Edinburgh Postnatal Depression Scale, respectively. Whole-brain connectivity was measured from 100 functionally defined regions of interest. Results: This study analyzed 59 resting-state functional connectivity magnetic resonance image data sets from the fetuses (mean [SD] gestational age, 33.52 [4 weeks]) of 50 healthy pregnant women (mean [SD] age, 33.77 [5.51]). Mean (SD) scores for the questionnaires were as follows: Spielberger State Anxiety Inventory, 26.66 (6.72) (range, 20-48); Spielberger Trait Anxiety Inventory, 28.09 (6.62) (range, 20-50); Perceived Stress Scale, 9.27 (5.13) (range, 1-25); and Edinburgh Postnatal Depression Scale 3.24 (2.84) (range, 0-14). Prenatal maternal anxiety scores measured using the Spielberger Trait and State Anxiety Inventories were associated with differences in fetal connectivity (Spielberger State Anxiety Inventory: pseudo-R2 = 0.019, P = .04; Spielberger Trait Anxiety Inventory: pseudo-R2 = 0.021, P = .007). Interhemispheric connections, such as those involving the parietofrontal and occipital association cortices, were associated with reduced maternal prenatal anxiety, and those between the brainstem and sensorimotor areas were associated with higher anxiety scores. Conclusions and Relevance: In this cohort study, an association was found between prenatal maternal anxiety and disturbances in fetal brain functional connectivity, suggesting altered fetal programming. Early onset of functional deviations suggests the need for more widespread screening of pregnant women for symptoms of anxiety.
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Connections that develop earlier (brainstem and sensorimotor areas) are stronger in high-anxiety states, while parieto-frontal and occipital connections that develop later are weaker.
“Connections that develop earlier (i.e., brainstem and sensorimotor areas) are stronger in high-anxiety states, while parieto-frontal and occipital connections that develop later are weaker.”
From Brain structural and functional outcomes in the offspring of women experiencing psychological distress during pregnancy (2024) · cites this paper as [33]
In healthy fetuses, in utero exposure to heightened maternal anxiety is linked to altered functional connectivity in sensorimotor and association cortices.
“In healthy fetuses, in utero exposure to heightened maternal anxiety is linked to altered functional connectivity in sensorimotor and association cortices.”
From Brain structural and functional outcomes in the offspring of women experiencing psychological distress during pregnancy (2024) · cites this paper as [33]
Increased hippocampal connectivity to medial and superior frontal gyri is present in fetuses of women with high trait anxiety.
“Increased hippocampal connectivity to medial and superior frontal gyri is also present in fetuses of women with high trait anxiety [33].”
From Brain structural and functional outcomes in the offspring of women experiencing psychological distress during pregnancy (2024) · cites this paper as [33]
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- Authors
- De Asis-Cruz, J., Krishnamurthy, D., Zhao, L., Kapse, K., Vezina, G., Andescavage, N., Quistorff, J., Lopez, C., & Limperopoulos, C.
- Affiliations
- Division of Diagnostic Imaging and Radiology, Children’s National, Washington DC
- Children's National (US)
- Corresponding author
- Limperopoulos, Catherine
- ORCID
- Venue
- JAMA Network Open
- Publisher
- American Medical Association (AMA)
- Published
- 2020-12-07
- Volume
- 3
- Issue
- 12
- Pages
- e2022349
- ISSN
- 2574-3805 (ISSN-L)
- PMC
- PMC12549102
- OpenAlex
- W3111635434
- Cited by
- 81
- References
- 91
- Citations by year
- 2026: 10 · 2025: 11 · 2024: 20 · 2023: 11 · 2022: 15 · 2021: 12 · 2020: 1
- FWCI
- 7.30
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- JAMA Network Open (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Heart, Lung, and Blood Institute (R01HL116585)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (U54HD090257)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Maternal Mental Health During Pregnancy and Postpartum
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Fetal and Pediatric Neurological Disorders
- Keywords
- maternal stress, maternal depression, fetal brain, resting-state functional connectivity, fetal brain development, interhemispheric connectivity, brainstem, gestational age
- MeSH terms
- Adult, Anxiety, Brain, Female, Gestational Age, Humans, Pregnancy, Pregnancy Complications, Prenatal Care, Prenatal Exposure Delayed Effects, Psychiatric Status Rating Scales, Stress, Psychological, Pregnant People, Fetal Development, Young Adult
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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