Maternal Adipokines Longitudinally Measured Across Pregnancy and their Associations with Neonatal Size, Length, and Adiposity

BACKGROUND/OBJECTIVES: Maternal obesity impacts fetal growth as early as 2(nd) trimester of pregnancy, yet little is known about the molecular mechanisms involved. We aimed to examine associations between maternal adipokines throughout pregnancy and neonatal size by pre-pregnancy obesity status. METHODS: In a prospective cohort of 2,802 U.S. pregnant women from the NICHD Fetal Growth Studies-Singleton Cohort (2009–2013) biospecimens were analyzed in a matched case-control subset of 321 women. Blood was collected at 10–14, 15–26 (fasting), 23–31, and 33–39 gestational weeks. Plasma leptin and soluble leptin receptor (sOB-R) and total and high-molecular-weight (HMW)-adiponectin were measured. Free leptin was calculated as leptin/sOB-R. Birthweight was abstracted from medical records. Neonatal length and skinfolds were measured. RESULTS: Leptin and sOB-R in late pregnancy tended to be positively and negatively associated with neonatal length, respectively, while free leptin throughout pregnancy tended to be positively associated with length. Free leptin associations with neonatal length were differential by obesity (i.e., inversely among women without obesity and positively among women with obesity). A per unit increase in free leptin at 33–39 weeks was associated with a shorter neonatal length by −0.55cm (95%CI −0.83, −0.28) in women without obesity and longer length by 0.49cm (95%CI 0.34, 0.65) in women with obesity. HMW-adiponectin at 33–39 weeks was inversely associated with neonatal length (β=−1.29cm; 95%CI, −1.74, −0.85) and skinfold thickness (β=−1.46mm; 95%CI, −1.58, −0.56) among women with obesity. Free leptin across pregnancy tended to be negatively associated with neonatal skinfold thickness among women without obesity, while free leptin in early pregnancy was positively associated with skinfold thickness. CONCLUSIONS: Maternal adipokines were associated with multiple pathways that influence neonatal size including length and adiposity, which differed in timing across pregnancy and by pre-pregnancy obesity. These findings provide new potential insights into mechanisms and timing by which maternal obesity may impact fetal growth.