Fetal-placental blood flow and neurodevelopment in childhood: a population-based neuroimaging study.

OBJECTIVES Antenatal Doppler measurements of fetal umbilical and cerebral circulations can predict perinatal complications, however, it is unclear if subtle variations in antenatal Doppler measures are associated with long-term neurodevelopmental outcomes. In this study, we examined whether antenatal Doppler measurements of fetal-placental and fetal cerebral circulations are associated with cognitive and motor ability and brain morphology in childhood. METHODS To evaluate the long-term sequelae of differences along a continuum of umbilical and cerebral artery circulation in the general population, we utilized a population-based longitudinal cohort study approach. In 2,803 mothers from the Generation R Study, we measured 2nd - and 3rd -trimester umbilical artery pulsatility index. In a subsample (n=602), we additionally measured 3rd -trimester anterior and middle cerebral artery pulsatility indices to calculate cerebroplacental ratios (cerebral divided by umbilical artery pulsatility index). Children underwent non-verbal intelligence testing at 4-8 years; and fingertapping tests measuring fine-motor skills, balance beam measuring gross-motor skills, and brain magnetic resonance imaging at 8-12 years. We assessed the relationships between prenatal Doppler ultrasound measures and neurodevelopmental outcomes using linear regression. We adjusted for child age, sex, maternal age, education, parity, and smoking. RESULTS Higher 3rd -trimester umbilical artery pulsatility index was associated with poorer fine-motor performance (0.41 fewer taps per one standard deviation higher umbilical artery pulsatility index, 95% Confidence Interval -0.70 to -0.11) and gross-motor performance (-0.64 steps, 95% Confidence Interval -1.08 to -0.20). Higher 3rd -trimester umbilical artery pulsatility index also associated with 0.65 points lower intelligence quotient (95% Confidence Interval -1.25 to -0.04): unlike associations with motor abilities, this finding did not survive correction for multiple testing. Higher 2nd -trimester umbilical artery pulsatility index was associated with smaller brain volume (-6.1 cm3 , 95% Confidence Interval -11.3 to -1.0), which did not survive correction for multiple testing. CONCLUSION Higher placental vascular resistance may have mild adverse effects on neurodevelopmental outcomes in school-age. While these effects are subtle at the population-level, we encourage future research into the role of early circulation in brain development. This could be used to develop targeted interventions. This article is protected by copyright. All rights reserved.