Prenatal Distress and Longitudinal Infant Functional Brain Development in a COVID-19 Pandemic Cohort

1737 

Abstract Submission 

Aliza Jaffer¹, Kathryn Manning¹, Gerald Giesbrecht¹, Lianne Tomfohr-Madsen², Catherine Lebel¹

¹University of Calgary, Calgary, Alberta, ²University of British Columbia, Vancouver, British Columbia

Aliza Jaffer, B.H.Sc.  
University of Calgary
Calgary, Alberta

Kathryn Manning, PhD  
University of Calgary
Calgary, Alberta

Gerald Giesbrecht, PhD  
University of Calgary
Calgary, Alberta

Lianne Tomfohr-Madsen, PhD  
University of British Columbia
Vancouver, British Columbia

Catherine Lebel, Ph.D.  
University of Calgary
Calgary, Alberta

Prenatal maternal psychological distress (i.e., anxiety and depression) can disrupt infant brain development and impact behaviour. During pregnancy, around 9-11% of individuals experience depression, while 18-25% experience elevated anxiety. The in-utero environment is directly influenced by prenatal distress. Such disruptions during critical periods of brain development may compromise developmental trajectories, potentially leading to lifelong consequences for cognitive, behavioural, and emotional functions in some children. Rates of psychological distress were substantially higher during the COVID-19 pandemic, raising concerns about its effect on infant development. We studied a cohort of pandemic-born infants and aimed to relate functional connectivity within brain networks across the first 2 years of life to prenatal distress and infant behaviour.

Mother-infant pairs were recruited from the Pregnancy during the COVID-19 Pandemic (PdP) study. Eligibility for the PdP study were being <35 weeks pregnant, living in Canada, ≥17 years of age, and able to read and write in English or French. Prenatal maternal distress was quantified using a combined factor of the Edinburgh Postnatal Depression Scale (EPDS) and the Patient Reported Outcomes Measurement Information System (PROMIS) Anxiety. Infant magnetic resonance imaging (MRI) was obtained at 3 months (n=63), 1 year (n=9), and 2 years (n=43) of age at the Alberta Children's Hospital using a GE 3T MR750w scanner with a 32-channel head coil (TR=2000 ms, TE=30 ms, voxel 3.6x3.6x3.6 mm³, flip angle=60º, 37 slices). 17 infants had scans for at least two timepoints. Parents assessed behaviour at 2 years using the Ages & Stages Questionnaire. MRI were preprocessed using FSL. MELODIC independent component analysis was used to remove volumes with excessive motion. Multi-session temporal concatenation was run using 3-month data to construct common spatial components and identify default mode (DMN), left frontoparietal (LFP), and executive control (EC) networks. Two regions of interest (ROIs) were defined in each network using 5 mm radii spheres placed at the hubs or peaks of connectivity networks (Figure 1): ROIs were in the anterior and posterior cingulate gyri (DMN), left angular gyrus and left precentral gyrus (LFP), and left and right superior frontal gyri (EC). Masks were generated using age-appropriate AAL atlases, where average time series were extracted and correlated for each subject to quantify functional connectivity within networks. Trajectories of connectivity and their relationship with prenatal distress were investigated using linear mixed effects models, including an interaction term between infant age and prenatal distress. Regression models were run to test relationships between distress, connectivity, and behaviour. Models were corrected for multiple comparisons using FDR.

Functional connectivity in the LFP network was significantly related to the interaction between age and prenatal distress (T=2.6, p=0.01, q=0.03, df=112) (Figure 2). Younger infants exposed to higher prenatal distress had weaker connectivity than infants exposed to lower prenatal distress; older infants exposed to higher prenatal distress had stronger connectivity than infants exposed to lower prenatal distress.

At 2 years of age, higher prenatal distress was related to stronger LFP network connectivity (T=2.8, p=0.008, q=0.024, df=39), and DMN connectivity was negatively associated with fine motor scores (T=-3.4, p=0.002, q=0.006, df=32).

Higher order cognitive networks, including the frontoparietal network, typically display immature connectivity patterns at birth that mature over time. Our findings reveal distinct patterns of functional connectivity within the LFP network, suggesting that infants exposed to higher prenatal distress have faster development. DMN connectivity may also affect fine motor ability, motivating the need for continued monitoring of these infants through childhood.

Psychiatric (eg. Depression, Anxiety, Schizophrenia) ²

Reasoning and Problem Solving

fMRI Connectivity and Network Modeling ¹

BOLD fMRI

Anxiety

FUNCTIONAL MRI

PEDIATRIC

Other - depression; perinatal period; behaviour; pregnancy; longitudinal development; brain networks; maternal health