44 - Prenatal SSRI exposure is associated with reduced regional fetal brain growth and cortical folding

Poster Number: 44
Publication Number: 44.621

Background: Untreated maternal depression and anxiety can adversely affect fetal brain development. Identifying safe treatment modalities for both mother and baby is crucial. While selective serotonin reuptake inhibitors (SSRIs) are commonly used to treat prenatal depression, available MRI studies show alterations in cerebral gray matter, amygdala, insula volumes, white matter microstructure, and brain functional connectivity in SSRI-exposed children. However, the impact of SSRI exposure on fetal brain volume and cortical folding remains unknown.

Objective: To compare global, regional, and tissue-specific volumetric brain growth and cortical folding in SSRI-exposed fetuses versus unexposed controls.

Design/Methods: We recruited pregnant women and performed structural MRI studies in SSRI-exposed and unexposed healthy low-risk fetuses. Fetal MRI was performed using a GE 1.5T scanner with 3D image reconstruction using slice-to-volume registration. Volumes of fetal total brain, cortical gray matter, white matter, deep gray matter, cerebellum, brainstem, and left and right hippocampus were quantified from deep learning based automatic segmentation and manual correction (Figure 1). Cortical folding included local gyrification index, sulcal depth, curvedness, and surface area. Fetal brain measures in SSRI-exposed group and unexposed fetuses were compared using Generalized Estimating Equation, adjusting for gestational age at MRI and sex.

Results: We studied 104 fetuses: 45 fetuses (67 scans) with SSRI exposure and 59 unexposed control fetuses (75 scans). Fetal brain MRI studies were performed between 17-39 weeks of gestation (mean: 30.69±4.83 weeks). The SSRI-exposed group showed significantly smaller volumes in white matter (94.04 vs 99.37 cm3, p= 0.02), deep gray matter (13.42 vs 14.08 cm3, p=0.009), left hippocampus (0.43 vs 0.52 cm3, p< 0.0001), and right hippocampus (0.47 vs 0.54 cm3, p< 0.0001) compared with unexposed controls (Table 1). Additionally, the SSRI-exposed group showed reduced cerebral cortical curvedness (0.21 vs 0.23 mm-1, p=0.0003) compared with unexposed controls.

Conclusion(s): We report for the first time impaired regional volumetric brain growth and cortical maturation in fetuses exposed to SSRIs in utero. The long-term neurodevelopmental consequences of these prenatal brain development disturbances is unknown and currently under study. Given the known effects of untreated maternal mental health disorders, future studies are warranted to identify safe and effective treatment paradigms for mother-infant dyads across the peripartum period.