Summary: Stress and anxiety during pregnancy are associated with impaired fetal cerebellar and hippocampal development in children with congenital heart disease.
Source: Children’s National Hospital
Knowing that your unborn fetus has congenital heart disease causes such pronounced maternal stress, anxiety and depression that these women’s fetuses end up with impaired development in key brain regions before they are born, according to research published online Jan. 13, 2020, in JAMA Pediatrics.
While additional research is needed, the Children’s National Hospital study authors say their unprecedented findings underscore the need for universal screening for psychological distress as a routine part of prenatal care and taking other steps to support stressed-out pregnant women and safeguard their newborns’ developing brains.
“We were alarmed by the high percentage of pregnant women with a diagnosis of a major fetal heart problem who tested positive for stress, anxiety and depression,” says Catherine Limperopoulos, Ph.D., director of the Center for the Developing Brain at Children’s National and the study’s corresponding author. “Equally concerning is how prevalent psychological distress is among pregnant women generally. We report for the first time that this challenging prenatal environment impairs regions of the fetal brain that play a major role in learning, memory, coordination, and social and behavioral development, making it all the more important for us to identify these women early during pregnancy to intervene,” Limperopoulos adds.
Congenital heart disease (CHD), structural problems with the heart, is the most common birth defect.
Still, it remains unclear how exposure to maternal stress impacts brain development in fetuses with CHD.
The multidisciplinary study team enrolled 48 women whose unborn fetuses had been diagnosed with CHD and 92 healthy women with uncomplicated pregnancies. Using validated screening tools, they found:
- 65% of pregnant women expecting a baby with CHD tested positive for stress
- 27% of women with uncomplicated pregnancies tested positive for stress
- 44% of pregnant women expecting a baby with CHD tested positive for anxiety
- 26% of women with uncomplicated pregnancies tested positive for anxiety
- 29% of pregnant women expecting a baby with CHD tested positive for depression and
- 9% women with uncomplicated pregnancies tested positive for depression
All told, they performed 223 fetal magnetic resonance imaging sessions for these 140 fetuses between 21 and 40 weeks of gestation. They measured brain volume in cubic centimeters for the total brain as well as volumetric measurements for key regions such as the cerebrum, cerebellum, brainstem, and left and right hippocampus.
Maternal stress and anxiety in the second trimester were associated with smaller left hippocampi and smaller cerebellums only in pregnancies affected by fetal CHD. What’s more, specific regions — the hippocampus head and body and the left cerebellar lobe – were more susceptible to stunted growth. The hippocampus is key to memory and learning, while the cerebellum controls motor coordination and plays a role in social and behavioral development.
The hippocampus is a brain structure that is known to be very sensitive to stress. The timing of the CHD diagnosis may have occurred at a particularly vulnerable time for the developing fetal cerebellum, which grows faster than any other brain structure in the second half of gestation, particularly in the third trimester.
“None of these women had been screened for prenatal depression or anxiety. None of them were taking medications. And none of them had received mental health interventions. In the group of women contending with fetal CHD, 81% had attended college and 75% had professional educations, so this does not appear to be an issue of insufficient resources,” Limperopoulos adds. “It’s critical that we routinely to do these screenings and provide pregnant women with access to interventions to lower their stress levels. Working with our community partners, Children’s National is doing just that to help reduce toxic prenatal stress for both the health of the mother and for the future newborns. We hope this becomes standard practice elsewhere.”
Adds Yao Wu, Ph.D., a research associate working with Limperopoulos at Children’s National and the study’s lead author: “Our next goal is exploring effective prenatal cognitive behavioral interventions to reduce psychological distress felt by pregnant women and improve neurodevelopment in babies with CHD.”
In addition to Limperopoulos and Wu , Children’s National study co-authors include Kushal Kapse, MS, staff engineer; Marni Jacobs, Ph.D., biostatistician; Nickie Niforatos-Andescavage, M.D., neonatologist; Mary T. Donofrio, M.D., director, Fetal Heart Program; Anita Krishnan, M.D., associate director, echocardiography; Gilbert Vezina, M.D., director, Neuroradiology Program; David Wessel, M.D., Executive Vice President and Chief Medical Officer; and Adré J. du Plessis, M.B.Ch.B., director, Fetal Medicine Institute. Jessica Lynn Quistorff, MPH, Catherine Lopez, MS and Kathryn Lee Bannantine, BSN, assisted with subject recruitment and study coordination.
Funding: Financial support for the research described in this post was provided by the National Institutes of Health under grant No. R01 HL116585-01 and the Thrasher Research Fund under Early Career award No. 14764.
Children’s National Hospital
Diedtra Henderson – Children’s National Hospital
The image is in the public domain.
Original Research: Closed access
“Association of Maternal Psychological Distress With In Utero Brain Development in Fetuses With Congenital Heart Disease”. Catherine Limperopoulos et al.
JAMA Pediatrics doi:10.1001/jamapediatrics.2019.5316.
Association of Maternal Psychological Distress With In Utero Brain Development in Fetuses With Congenital Heart Disease
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.
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.
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.
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.