Structural Changes of the Human Fetal Brain During the COVID-19 Pandemic

Background: Elevated maternal psychological distress during pregnancy is linked to adverse short- and long-term outcomes in the offspring. The potential deleterious effects of intensified levels of maternal distress during the COVID-19 pandemic on the developing fetal brain are currently unknown.Methods: We prospectively enrolled 202 pregnant women: 65 with negative COVID-19 diagnoses during the pandemic who underwent 92 fetal MRI scans, and 137 pre-pandemic controls who had 182 MRI scans. Multi-plane, multi-phase single shot fast spin echo T2-weighted images were acquired on a GE 1.5T MRI Scanner. High-resolution 3D models of the fetal brains were reconstructed, and volumes of six brain tissue types were calculated: cortical gray matter (CGM), white matter (WM), cerebellum, deep gray matter (DGM), brainstem, and hippocampus. Cortical folding measures, including brain surface area, local gyrification index (LGI), and sulcal depth were determined. At each MRI scan, maternal distress was assessed using validated stress, anxiety and depression scales. Generalized estimating equations (GEEs) were utilized to compare maternal distress measures, brain volume and cortical folding differences between pandemic and pre-pandemic cohorts.Findings: Stress and depression scores were significantly higher in the pandemic cohort (14.2 vs. 10.4 for stress; 5.9 vs. 4.2 for depression; p<0.01). Fetal WM, hippocampal, and cerebellar volumes were decreased in the pandemic cohort (p<0.01). Cortical surface area and LGI were also decreased in all four lobes (p<0.01), while sulcal depth was lower in the frontal, parietal, and occipital lobes (p<0.05) in the pandemic cohort, indicating delayed brain gyrification.Conclusion: We relate heightened maternal psychological distress with impaired fetal brain growth and delayed cerebral cortical gyrification in COVID-19 pandemic era pregnancies. The potential long-term neurodevelopmental consequences of altered fetal brain development in COVID-era pregnancies complicated by elevated maternal distress merit further study.Funding: This study was funded by National Institutes of Health (NHLBI R01 HL116585-01), Intellectual and Developmental Disabilities Research Center (IDDRC), and A. James & Alice B. Clark Foundation.Declaration of Interest: None to declare. Ethical Approval: These studies received ethical approval from Children's National Hospital Institutional Review Board (Protocol: 1373 and 14257).