Metabolic expenditure, neurodevelopment, and weight gain into early childhood after fetal growth restriction

Fetal growth restriction (FGR) subjects exhibit altered metabolism, with higher metabolic rate due to their small body mass, and by adopting strategies to minimise energy expenditure. We investigated how these metabolic differences develop, or manifest in growth trajectories, after FGR, small for gestational age (SGA) (constitutionally small), and normal pregnancies. We curated a unique composite dataset of 1934 subjects between 14 weeks of gestation and 5 years of age. First, we assessed fetal and infant heart rate to assess whether higher metabolic rate persisted postnatally after FGR. Next, as the largest energy expenditure is brain synaptic maintenance, we tested whether FGR infants had lower white matter volume (proxy for synapse number). Finally, we modelled longitudinal body weight into childhood in FGR, SGA, and control groups, and tested for associations with neurodevelopmental scores at 1-2 years. Heart rate at rest was higher in FGR fetuses and infants (688 subjects), and FGR infants exhibited a blunted capacity to increase heart rate to a nociceptive procedure (i.e. a physiological challenge). FGR infants had smaller white matter volume (270 subjects). Finally, the more an individuals weight gain deviated below average curves (1714 subjects), the lower were their motor and cognitive scores at 1-2 years.