Maternal Circulating Placental Growth Factor and Neonatal Metabolic Health Biomarkers in Small for Gestational Age Infants

Small for gestational age (SGA) infants are at increased risk of type 2 diabetes in adulthood. It is unknown whether any prenatal biomarkers are helpful for identifying SGA infants with altered metabolic health profile at birth or later life. In a nested study of 162 SGA (birth weight < 10th percentile) and 161 optimal birth weight (25th–75th percentiles) control infants in the 3D (design, develop and discover) birth cohort in Canada, we assessed whether maternal circulating placental growth factor (PlGF), a biomarker of placental function, is associated with metabolic health biomarkers in SGA infants. Main outcomes were cord plasma insulin, proinsulin, insulin-like growth factor-I (IGF-I), leptin, and high-molecular weight (HMW) adiponectin concentrations. Maternal PlGF concentrations at 32–35 weeks of gestation were substantially lower in SGA versus control infants (P < 0.001), so as were cord plasma proinsulin (P = 0.005), IGF-I (P < 0.001), leptin (P < 0.001), and HMW adiponectin (P = 0.002) concentrations. In SGA infants with both low (<25th percentile) and normal maternal PlGF concentrations, cord plasma IGF-I and leptin concentrations were lower than control infants, but the decreases were to a greater extent in SGA infants with low maternal PlGF. Cord blood leptin levels were lower comparing SGA infants with low vs. normal maternal PlGF levels (P = 0.01). SGA infants with low maternal circulating PlGF levels at late gestation were characterized by greater decreases in cord blood IGF-I and leptin concentrations. Maternal circulating PlGF appears to be associated with neonatal metabolic health profile in SGA infants.