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Original Investigation
January 13, 2020

Association of Maternal Psychological Distress With In Utero Brain Development in Fetuses With Congenital Heart Disease

Author Affiliations
  • 1Center for the Developing Brain, Children’s National Health System, Washington, DC
  • 2Division of Biostatistics and Study Methodology, Children’s Research Institute, Children’s National Health System, Washington, DC
  • 3Division of Neonatology, Children’s National Health System, Washington, DC
  • 4Division of Cardiology, Children’s National Health System, Washington, DC
  • 5Department of Diagnostic Imaging and Radiology, Children’s National Health System, Washington, DC
  • 6Hospital and Specialty Services, Children’s National Health System, Washington, DC
  • 7Fetal Medicine Institute, Children’s National Health System, Washington, DC
JAMA Pediatr. Published online January 13, 2020. doi:10.1001/jamapediatrics.2019.5316
Key Points

Question  Is there an association of prenatal maternal stress, anxiety, and depression with brain growth in fetuses with congenital heart disease?

Findings  This longitudinal case-control study of 140 fetuses, including 48 fetuses with congenital heart disease having 74 magnetic resonance imaging scans and 92 healthy fetuses with 149 magnetic resonance imaging scans, showed that psychological distress in women with fetal congenital heart disease appears to be prevalent and associated with impaired fetal cerebellar and hippocampal development during the second half of gestation.

Meaning  This study’s findings suggest that universal screening for prenatal psychological distress and integrated cognitive-behavioral interventions are needed to better support pregnant women and optimize neurodevelopment in fetuses with congenital heart disease.


Importance  Prenatal maternal psychological distress can result in detrimental mother and child outcomes. Maternal stress increases with receipt of a prenatal diagnosis of fetal congenital heart disease (CHD); however, the association between maternal stress and the developing brain in fetuses with CHD is unknown.

Objective  To determine the association of maternal psychological distress with brain development in fetuses with CHD.

Design, Setting, and Participants  This longitudinal, prospective, case-control study consecutively recruited 48 pregnant women carrying fetuses with CHD and 92 healthy volunteers with low-risk pregnancies from the Children’s National Health System between January 2016 and September 2018. Data were analyzed between January 2016 and June 2019.

Exposures  Fetal CHD and maternal stress, anxiety, and depression.

Main Outcomes and Measures  Maternal stress, anxiety, and depression were measured using the Perceived Stress Scale, Spielberger State-Trait Anxiety Inventory, and Edinburgh Postnatal Depression Scale, respectively. Volumes of fetal total brain, cerebrum, left and right hippocampus, cerebellum, and brainstem were determined from 3-dimensionally reconstructed T2-weighted magnetic resonance imaging (MRI) scans.

Results  This study included 223 MRI scans from 140 fetuses (74 MRIs from 48 fetuses with CHD and 149 MRIs from 92 healthy fetuses) between 21 and 40 weeks’ gestation. Among 48 women carrying fetuses with CHD, 31 (65%) tested positive for stress, 21 (44%) for anxiety, and 14 (29%) for depression. Among 92 pregnant women carrying healthy fetuses, 25 (27%) tested positive for stress, 24 (26%) for anxiety, and 8 (9%) for depression. Depression scores were higher among 17 women carrying fetuses with single-ventricle CHD vs 31 women carrying fetuses with 2-ventricle CHD (3.8; 95% CI, 0.3 to 7.3). Maternal stress and anxiety were associated with smaller left hippocampal (stress: −0.003 cm3; 95% CI, −0.005 to −0.001 cm3), right hippocampal (stress: −0.004; 95% CI, −0.007 to −0.002; trait anxiety: −0.003; 95% CI, −0.005 to −0.001), and cerebellar (stress: −0.06; 95% CI, −0.09 to −0.02) volumes only among women with fetal CHD. Impaired hippocampal regions were noted in the medial aspect of left hippocampal head and inferior aspect of right hippocampal head and body. Impaired cerebellar regions were noted in the anterior superior aspect of vermal and paravermal regions and the left cerebellar lobe.

Conclusions and Relevance  These findings suggested that psychological distress among women carrying fetuses with CHD is prevalent and is associated with impaired fetal cerebellar and hippocampal development. These data underscore the importance of universal screening for maternal psychological distress, integrated prenatal mental health support, and targeted early cognitive-behavioral interventions given that stress is a potentially modifiable risk factor in this high-risk population.

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    1 Comment for this article
    Social Cohesion
    Paul Nelson, M.D., M.S. | Family Health Care, P.C. retired
    The findings may represent the effects of upstream deficits in social cohesion that could presumably prevent, ameliorate, or mitigate maternal resiliency for counter-balancing the presence of congenital heart disease on fetal baseline homeostasis, especially on the circulatory support for brain development. The micro-social dilemmas that each person endures every day have become especially harmful for women who are enduring or may need to endure a pregnancy.

    In the midst of pursuing the scientific and humanitarian mandates for healthcare, we must acknowledge the uniquely local ecologic and cultural traditions that underly each community's social cohesion. I am
    continually reminded that trust and self-reported health have been shown to exhibit reverse causality. See Giordano GN, et al. J. Epidemiol Community Health 2015; dx.doi.org/10.1136/jech-2015-205822

    It seems that the Kaizen Paradox underlies our current strategy for healthcare reform. Formulated by Professor Oren Harari (1949-2010), it states that "The electric light bulb did not come from the continuous improvement of candles."