Abstract
Prenatal maternal stress is increasingly associated with adverse outcomes in pregnant women and their offspring. However, the association between maternal stress and human fetal brain growth and metabolism is unknown. To identify the association between prenatal maternal psychological distress and fetal brain growth, cortical maturation, and biochemical development using advanced 3-dimensional volumetric magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy (1H-MRS). This cohort study prospectively recruited pregnant women from low-risk obstetric clinics in Washington, DC, from January 1, 2016, to April 17, 2019. Participants were healthy volunteers with a normal prenatal medical history, no chronic or pregnancy-induced physical or mental illnesses, and normal results on fetal ultrasonography and biometry studies. Fetal brain MRI studies were performed at 2 time points between 24 and 40 weeks' gestation. Prenatal maternal stress, anxiety, and depression. Volumes of fetal total brain, cortical gray matter, white matter, deep gray matter, cerebellum, brainstem, and hippocampus were measured from 3-dimensional reconstructed T2-weighted MRI scans. Cortical folding measurements included local gyrification index, sulcal depth, and curvedness. Fetal brain N-acetylaspartate, creatine, and choline levels were quantified using 1H-MRS. Maternal stress, depression, and anxiety were measured with the Perceived Stress Scale (PSS), Edinburgh Postnatal Depression Scale (EPDS), Spielberger State Anxiety Inventory (SSAI), and Spielberger Trait Anxiety Inventory (STAI). A total of 193 MRI studies were performed in 119 pregnant women (67 [56%] carrying male fetuses and 52 [44%], female fetuses; maternal mean [SD] age, 34.46 [5.95] years) between 24 and 40 gestational weeks. All women were high school graduates, 99 (83%) were college graduates, and 100 (84%) reported professional employment. Thirty-two women (27%) had positive scores for stress, 31 (26%) for anxiety, and 13 (11%) for depression. Maternal trait anxiety was associated with smaller fetal left hippocampal volume (STAI score: -0.002 cm3; 95% CI, -0.003 to -0.0008 cm3; P = .004). Maternal anxiety and stress were associated with increased fetal cortical gyrification in the frontal lobe (β for SSAI score: 0.004 [95% CI, 0.001-0.006; P = .002]; β for STAI score: 0.004 [95% CI, 0.002-0.006; P < .001]; β for PSS score: 0.005 [95% CI, 0.001-0.008; P = .005]) and temporal lobe (β for SSAI score: 0.004 [95% CI, 0.001-0.007; P = .004]; β for STAI score: 0.004 [95% CI, 0.0008-0.006; P = .01]). Elevated maternal depression was associated with decreased creatine (EPDS score: -0.04; 95% CI, -0.06 to -0.02; P = .005) and choline (EPDS score: -0.03; 95% CI, -0.05 to -0.01; P = .02) levels in the fetal brain. This study found that the prevalence of maternal psychological distress in healthy, well-educated, and employed pregnant women was high, underappreciated, and associated with impaired fetal brain biochemistry and hippocampal growth as well as accelerated cortical folding. These findings appear to support the need for routine mental health surveillance for all pregnant women and targeted interventions in women with elevated psychological distress.
Highlights
Perinatal mental health problems are a major public health issue and are associated with detrimental and enduring consequences on maternal and child health.[1,2,3,4] Depression and anxiety are the most common mental health problems during pregnancy, prevalence rates vary by population characteristics, timing, and type of screening used
Maternal anxiety and stress were associated with increased fetal cortical gyrification in the frontal lobe (β for Spielberger State Anxiety Inventory (SSAI) score: 0.004 [95% CI, 0.001-0.006; P = .002]; β for Spielberger Trait Anxiety Inventory (STAI) score: 0.004 [95% CI, 0.002-0.006; P < .001]; β for Perceived Stress Scale (PSS) score: 0.005 [95% CI, 0.001-0.008; P = .005]) and temporal lobe (β for SSAI score: 0.004 [95% CI, 0.001-0.007; P = .004]; β for STAI score: 0.004 [95% CI, 0.0008-0.006; P = .01])
This study found that the prevalence of maternal psychological distress in healthy, well-educated, and employed pregnant women was high, underappreciated, and associated with impaired fetal brain biochemistry and hippocampal growth as well as accelerated cortical folding
Summary
Perinatal mental health problems are a major public health issue and are associated with detrimental and enduring consequences on maternal and child health.[1,2,3,4] Depression and anxiety are the most common mental health problems during pregnancy, prevalence rates vary by population characteristics, timing, and type of screening used. Maternal mental health problems in pregnancy have been associated with an elevated risk for spontaneous abortion,[10] preeclampsia,[11] preterm delivery,[12] and lower birth weight.[13] Adverse child outcomes are increasingly reported across the spectrum of learning,[14] behavioral[4] and interpersonal problems, and neuropsychiatric dysfunction.[15] Differences in human brain development have been described in the postnatal months and years after intrauterine exposure to maternal psychological distress during pregnancy These findings have included smaller head circumference,[13] reduced cerebral and cerebellar gray matter volume,[16,17,18] increased amygdala[19,20] and decreased hippocampal volumes,[21] and altered brain microstructure[22,23] and connectivity.[24,25] disturbances in brain biochemicals have been reported in animal studies, including reductions in N-acetylaspartate (NAA; a marker of neuronal integrity) in the frontal cortex and hypothalamus in early life stress–exposed mice[26,27,28] as well as altered neurotransmitter metabolism of γ-aminobutyric acid and glutamate in the right hippocampus of pregestational stress–exposed offspring.[29] a growing body of evidence finds a correlation between prenatal maternal psychological distress and neurodevelopmental dysfunction in their offspring, the association of psychological distress with fetal brain development and metabolism remains poorly understood at this time
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