Fetal–placental blood flow and neurodevelopment in childhood: population‐based neuroimaging study

OBJECTIVE: Antenatal Doppler measurements of the fetal umbilical and cerebral circulations can predict perinatal complications; however, it is unclear if subtle variations in antenatal Doppler measurements are associated with long‐term neurodevelopmental outcome. In this study, we examined whether antenatal Doppler measurements of the fetal–placental circulation are associated with cognitive and motor abilities and brain morphology in childhood. METHODS: To evaluate differences in long‐term sequelae across the continuum of the umbilical and cerebral artery circulations in the general population, we utilized a population‐based longitudinal cohort study approach. In women from the Generation R study, we measured second‐ and third‐trimester umbilical artery pulsatility index (UA‐PI). Children underwent non‐verbal intelligence testing at 4–8 years of age, and at 8–12 years they underwent finger‐tapping tests to measure fine motor skills, balance beam tests to measure gross motor skills and brain magnetic resonance imaging. We assessed the relationships between prenatal UA‐PI and neurodevelopmental outcome using linear regression. We adjusted for child age and sex, maternal age, education, parity and smoking status. RESULTS: The study sample included 2803 pregnancies. Higher third‐trimester UA‐PI was associated with poorer fine motor performance (0.41 (95% CI, 0.11–0.70) fewer taps on the finger‐tapping test per 1 SD higher UA‐PI) and gross motor performance (0.64 (95% CI, 0.20–1.08) fewer steps on the balance beam test per 1 SD higher UA‐PI). One SD higher third‐trimester UA‐PI was also associated with 0.65 (95% CI, 0.04–1.25) points lower intelligence quotient; however, unlike the associations with motor abilities, this finding did not persist after correction for multiple testing. Higher second‐trimester UA‐PI was associated with smaller brain volume (6.1 (95% CI, 1.0–11.3) cm(3) reduction per 1 SD higher UA‐PI), but the association did not persist after correction for multiple testing. CONCLUSION: Higher placental vascular resistance may have mild adverse effects on neurodevelopmental outcome at school age. While these effects are subtle at population level, we encourage future research into the role of early circulation in brain development. This information could be used to develop targeted interventions. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.