Psychological Distress Affects Unborn Fetus Brain Development


Investigators find an association between fetuses with congenital heart disease and impaired fetal hippocampal and cerebellar development.

Catherine Limperopoulos, PhD

Catherine Limperopoulos, PhD

Prenatal psychological distress among women whose fetuses have congenital heart disease (CHD) can lead to damaging outcomes for both the mother and child.

New research from a team of investigators, led by Catherine Limperopoulos, PhD, the director of the Center for the Developing Brain at the Children’s National Hospital, analyzed women whose unborn fetuses had been diagnosed with CHD and those without. The team aimed to determine the link between maternal psychological distress with brain development in fetuses with the disease.

Limperopoulos and colleagues found that women who knew their unborn fetus had CHD had increased maternal stress, anxiety, and depression which led to impaired development in key brain regions of the fetus.

The findings suggest that universal screening for psychological distress is needed as a routine part of prenatal care, Limperopoulos said in a statement.

The investigators recruited 48 pregnant women who carried fetuses with CHD and 92 healthy women with low-risk pregnancies between January 2016—September 2018. Psychological distress was measured using questionnaires, including the Perceived Stress Scale (score of ≥15 indicating higher than average stress), the Edinburgh Postnatal Depression Scale (score of ≥10 indicating presence of depressive symptoms during pregnancy), and Spielberger State-Trait Anxiety Inventory (score of ≥40 indicating symptoms of anxiety).

Overall, the team included 223 fetal MRI scans from 140 pregnant women—48 women with fetal CHD with 74 MRI scans and 92 healthy fetuses with 149 MRI scans. The mean gestational age during the MRI was 32.1 weeks (range, 21.6—38.3 weeks) for fetuses with CHD and 32.4 weeks (24.1–39.4 weeks) for healthy fetuses.

Of the women with fetal CHD, 65% tested positive for stress, 44% were positive for anxiety, and 29% tested positive for depression. Among the women with healthy pregnancies, 27% tested positive for stress, 26% for anxiety, and 9% for depression.

Women carrying fetuses with CHD had significantly higher prenatal stress (PSS score difference, 5.3; 95% CI, 3.0—7.5), anxiety (SSAI score difference, 7.5; 95% CI, 3.5–11.4), and depression (EPDS score difference, 3.3; 95% CI, 1.7–4.9) compared with those whose fetuses were healthy. The mean depression score was significantly higher (3.8; 95% CI, .3–7.3) among women with single ventricle vs two-ventricle fetal CHD.

There was a linear increase in fetal brain volumes with increased gestational age in both healthy fetuses and those with CHD. For the fetuses with CHD, males showed faster growth rates than females for total brain volume (18.6 vs 16.1 cm3/week), cerebrum volume (17.1 vs 14.8 cm3/week), and cerebellum volume (1.3 vs 1.1 cm3/week).

In both fetuses with CHD and in healthy fetuses, right hippocampus volumes were significantly larger than left hippocampus volumes (CHD: .03 cm3; 95% CI, .02—.05 cm3; controls: .04 cm3; 95% CI, .03—.05 cm3). Among fetuses with CHD, brain volume did not significantly differ in single-ventricle vs two-ventricle CHD. Total brain volume and cerebrum volume were smaller in single-ventricle vs two-ventricle CHD.

Elevated stress for the mother was significantly linked with smaller fetal cerebellum volumes for women whose fetus had CHD (−.06 cm3; 95% CI, −0.09 to −0.02 cm3), left hippocampus (−.003 cm3; 95% CI, −.005 to −.001 cm3), and right hippocampus (−.004 cm3; 95% CI, −.007 to −.002 cm3). What’s more, maternal trait anxiety was significantly associated with smaller right hippocampus volumes (−.003 cm3; 95% CI, −.005 to −.001 cm3).

In women with healthy fetuses, maternal trait anxiety was negatively associated with fetal left hippocampus and right hippocampus volumes.

The findings suggest that psychological distress—including stress, anxiety, and depression—are prevalent and clinically underappreciated in women carrying fetuses with CHD. There is also an association with impaired fetal hippocampal and cerebellar development in fetuses with the disease.

Additional research is needed to study the association of fetal brain development with psychological distress in pregnant women who receive a fetal anomalies diagnosis.

The study, “Association of Maternal Psychological Distress With In Utero Brain Development in Fetuses With Congenital Heart Disease,” was published online in the journal JAMA Pediatrics.

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