Abstract
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. To investigate the association between prenatal maternal stress, anxiety, and depression and in vivo fetal brain resting state functional connectivity. 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. Maternal stress, anxiety, and depression. 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. 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. 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.
Highlights
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)
In this cohort study, an association was found between prenatal maternal anxiety and disturbances in fetal brain functional connectivity, suggesting altered fetal programming
Using multivariate distance matrix regression (MDMR), we examined the association between maternal psychological distress using well-validated self-report questionnaires and the developing connections in the human fetal brain
Summary
Up to 50% of women report symptoms of stress, depression, or anxiety during pregnancy based on systematic reviews.[1,2,3] Maternal mental health disorders are associated with adverse pregnancy outcomes and an increased risk for neuropsychiatric disorders, such as autism and attention-deficit/ hyperactivity disorder.[4,5,6,7] The high prevalence of prenatal psychological distress and its association with poor obstetric outcomes as well as motor deficits, sociocognitive, and socioaffective impairments in exposed children underscores the need for identifying the earliest effects of in utero exposure to the developing brain.Available clinical and imaging evidence supports the negative association of maternal stress with postnatal growth and brain development. Clinical studies have reported neurobehavioral deficits beginning in infancy and early childhood, including higher reactivity,[10] impaired motor coordination,[11] and language delays.[12] Postnatal brain imaging findings have provided insights into potential neural substrates for these deficits These include reduced cortical thickness,[13,14] amygdala and hippocampal volume changes,[15,16,17] asymmetric electroencephalographic patterns in the frontal lobes,[18,19] white matter microstructural changes,[20,21] and impaired connectivity.[22,23] More recently, a study by Wu and colleagues[24] provided, to our knowledge, the first report of impaired brain metabolism, reduced hippocampal growth, and accelerated cortical folding in fetuses of women experiencing psychological distress. The effect of prenatal maternal stress on the developing neural circuitry during this critical period of brain development has not been investigated
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