Abstract 18334: Altered in-vivo Placental Microstructure Predicts Adverse Neurodevelopmental Outcomes in Toddlers With Congenital Heart Disease

Abstract

Introduction: Pregnancies complicated by fetal congenital heart disease (CHD) are at risk for disrupted placenta function; placental insufficiency, in turn, is a risk factor that may adversely impact offspring neurodevelopment. However, the relationship between altered in-vivo placenta function and infant neurobehavioral outcomes in CHD is unknown. Hypothesis: We hypothesized that altered in-vivo placenta microstructural diffusion in CHD would be associated with impaired infant neurodevelopment. Methods: We prospectively recruited women with pregnancies complicated by CHD diagnosis and low-risk pregnancies. Women underwent an MRI on a GE 1.5T scanner at 20-39 gestational weeks. T2w sequence and pulsed gradient spin echo were acquired for placenta volume and diffusion kurtosis measures. Bayley-III and Infant-Toddler Social and Emotional Assessment were completed at around 18 months. Generalized estimating equation was used to examine the association between placenta measures and infant outcomes, adjusting for potential confounders. Results: We enrolled 236 mother/baby dyads (111 CHD; 125 controls) who underwent 394 MRIs (175 CHD; 219 controls). Forty-seven had single-ventricle (SV) CHD and 64 had two-ventricle (2V) CHD. In CHD, 32 subjects died, and 71 infants had neurodevelopment testing at a mean age of 20 months. Placenta diffusion coefficient (dki_d), reflecting tissue cellularity, was higher in CHD vs controls (p=0.009). In CHD, placenta diffusional kurtosis (dki_k), reflecting tissue heterogeneity, was lower in neonates who died pre-operatively vs those who survived (p=0.05). Compared to 2V CHD, pregnancies with SV fetuses had lower placenta dki_k and trending higher placenta dki_d. In CHD, higher placenta dki_d was associated with poorer language skills (p=0.05) while lower placenta dki_k was associated with higher behavioral dysregulation (p=0.03). Conclusions: We report for the first time disturbances in placenta microstructural diffusion in CHD. We also demonstrate that altered placenta diffusion was associated with impaired language and behavioral dysregulation in CHD toddlers. These data suggest that altered placenta microstructure may be an important biomarker for later neurodevelopmental dysfunction in CHD.