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) with no evidence of FGR, and normal pregnancies. We curated a unique composite dataset of subjects between 14 weeks of gestation and six 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 3.2 beats per minute higher in FGR fetuses and infants (710 subjects), and FGR infants exhibited only 52% the increase in heart rate to a nociceptive procedure (i.e. a physiological challenge) observed in controls. FGR infants had 7 cm³ smaller white matter volume (270 subjects). Finally, for every - 100 g an individual's weight deviated below their group's average (1660 subjects), their motor score was 0.4 points lower (1030 subjects). FGR subjects continue to exhibit metabolic differences long after birth, which may further disadvantage them beyond the initial antenatal insult. Growth trajectories encode information about how FGR is transmitted into suboptimal neurodevelopment, and could identify intervention opportunities.