An antenatal marker of neurodevelopmental outcomes in infants with congenital heart disease

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Prenatal exposures are known to alter fetal neurodevelopment and autonomic control. We aimed to explore the correlation between fetal autonomic activity, measured by fetal heart rate variability, and 18-month developmental outcome in subjects with congenital heart disease.


From 2010 to 2013, 5 fetuses with hypoplastic left heart syndrome, 9 with transposition of the great arteries and 9 with tetralogy of Fallot were included in this prospective cohort study. A maternal abdominal fetal electrocardiogram monitor recorded fetal heart rate at 34 to 38 weeks gestational age. We assessed associations between fetal heart rate parameters including interquartile range and s.d. of the fetal RR intervals and 18-month Bayley Scales of Infant Development-III scores using Pearson's correlation coefficient. Multivariable regression modeling identified predictors of neurodevelopmental scores.


Fetal heart rate variability parameters at 34 to 38 weeks gestational age correlated with 18-month Cognition (r = 0.47, P = 0.03) and Motor scores (r = 0.66, P = 0.001). The interquartile range of the fetal RR intervals predicted Cognition (β = 0.462, P = 0.028, R2 = 0.282) and Motor (β = 0.637, P < 0.001, R2 = 0.542) scores.


In fetuses with congenital heart disease, low heart rate variability at 34 to 38 weeks gestational age predicts diminished 18-month Cognitive and Motor performance. Prenatal autonomic activity may serve as a marker of early childhood development in these high-risk patients.

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