Neurodevelopment following fetal growth restriction and its relationship with antepartum parameters of placental dysfunction

TLDR: Observational and management studies do not suggest that fetal deterioration has an independent impact on neurodevelopment in early‐onset FGR, and further research needs to establish benefits of perinatal intervention, as the pattern of vulnerability and effects of fetal deterioration appear to differ in the third trimester.

Abstract: Placental dysfunction leading to fetal growth restriction (FGR) is an important risk factor for neurodevelopmental delay. Recent observations clarify that FGR evolves prenatally from a preclinical phase of abnormal nutrient and endocrine milieu to a clinical phase that differs in characteristics in preterm and term pregnancies. Relating childhood neurodevelopment to these prenatal characteristics offers potential advantages in identifying mechanisms and timing of critical insults. Based on available studies, lagging head circumference, overall degree of FGR, gestational age, and umbilical artery (UA), aortic and cerebral Doppler parameters are the independent prenatal determinants of infant and childhood neurodevelopment. While head circumference is important independent of gestational age, overall growth delay has the greatest impact in early onset FGR. Gestational age has an overriding negative effect on neurodevelopment until 32-34 weeks' gestation. Accordingly, the importance of Doppler status is demonstrated from 27 weeks onward and is greatest when there is reversed end-diastolic velocity in the UA or aorta. While these findings predominate in early-onset FGR, cerebral vascular impedance changes become important in late onset FGR. Abnormal motor and neurological delay occur in preterm FGR, while cognitive effects and abnormalities that can be related to specific brain areas increase in frequency as gestation advances, suggesting different pathophysiology and evolving vulnerability of the fetal brain. Observational and management studies do not suggest that fetal deterioration has an independent impact on neurodevelopment in early-onset FGR. In late-onset FGR further research needs to establish benefits of perinatal intervention, as the pattern of vulnerability and effects of fetal deterioration appear to differ in the third trimester.