Fetal cerebrovascular resistance and neonatal EEG predict 18-month neurodevelopmental outcome in infants with congenital heart disease.

OBJECTIVES The purpose of this study was to investigate early markers of risk for neurobehavioral compromise in survivors with congenital heart disease (CHD). METHODS Pregnant women in whom a fetal CHD had been diagnosed before 24 weeks' gestational age (GA) were enrolled in this prospective pilot study for serial Doppler ultrasound assessment of the fetal middle cerebral artery (MCA) and umbilical arteries. The cerebral-to-placental resistance ratio (CPR) and MCA pulsatility index (PI) Z-scores for GA were calculated. After birth, subjects underwent high-density (128-lead) electroencephalography (EEG), and beta frequency (12-24 Hz) band EEG power, a measure of local neural synchrony, was analyzed. Neurodevelopment was assessed at 18 months with the Bayley Scales of Infant Development (BSID)-III. RESULTS Thirteen subjects were enrolled: four with hypoplastic left heart syndrome (HLHS), four with transposition of the great arteries (TGA) and five with tetralogy of Fallot (TOF). Compared with subjects with normal CPR, those with CPR < 1 (n = 7) had lower mean BSID cognitive scores (91.4 ± 4.8 vs. 99.2 ± 3.8, P = 0.008). Fetal MCA-PI Z-score also correlated with BSID cognitive score (r = 0.589, P = 0.03) as did neonatal EEG left frontal polar (r = 0.58, P = 0.037) and left frontal (r = 0.77, P = 0.002) beta power. Furthermore, fetal Doppler measures were associated with EEG power: fetuses with CPR < 1 had lower left frontal polar (t = 2.36, P = 0.038) and left frontal (t = 2.85, P = 0.016) beta power as newborns than did fetuses with normal CPR, and fetal MCA-PI Z-score correlated with neonatal EEG left frontal polar (r = 0.596, P = 0.04) and left frontal (r = 0.598, P = 0.04) beta power. CONCLUSION In fetuses with HLHS, TGA and TOF, abnormal cerebrovascular resistance predicts decreased neonatal EEG left frontal beta power and lower 18-month cognitive development scores.