Neonatal Leptin Levels Predict the Early Childhood Developmental Assessment Scores of Preterm Infants

Preterm infants have low circulating levels of leptin, a key trophic hormone that influences growth and development. While the clinical importance of prematurity-associated leptin deficiency is undefined, recent preclinical and clinical investigations have shown that targeted enteral leptin supplementation can normalize neonatal leptin levels. We tested the hypothesis that, independent of growth velocity, prematurity-related neonatal leptin deficiency predicts adverse cardiovascular and neurodevelopmental outcomes. In a planned 2-year longitudinal follow-up of 83 preterm infants born at 22 to 32 weeks' gestation, we obtained blood pressures from 58 children and the Ages & Stages Questionnaire (ASQ-3) for 66 children. Based on univariate analysis, blood pressures correlated with gestational age at birth (R = 0.30, p < 0.05) and weight gain since discharge (R = 0.34, p < 0.01). ASQ-3 scores were significantly higher in female than male children. Utilizing best subset regression with Mallows' C_p as the criterion for model selection, higher systolic blood pressure was predicted by rapid postnatal weight gain, later gestation at delivery and male sex (C_p = 3.0, R = 0.48). Lower ASQ-3 was predicted by lower leptin levels at 35 weeks postmenstrual age, earlier gestation at delivery and male sex (C_p = 2.9, R = 0.45). Children that had leptin levels above 1500 pg/mL at 35 weeks postmenstrual age had the highest ASQ-3 scores at 2 years. In conclusion, independent of growth velocity, higher leptin levels at 35 weeks' gestation are associated with better developmental assessment scores in early childhood. While longer-term follow-up of a larger cohort is needed, these findings support investigations that have suggested that targeted neonatal leptin supplementation could improve the neurodevelopmental outcomes of preterm infants.