Abstract Adequate maternal thyroid hormone (TH) is necessary for fetal brain development. The role of placental human chorionic gonadotropin (hCG) in ensuring the production of TH is less well understood. The objective of the study was to evaluate 1) associations of placental hCG and its subunits, and maternal TH in the second trimester, and 2) the single and joint effects of TH and placental hormones on cognitive development and communication at ages 1 and 3 years. Fifty individuals (5%) were selected from the CANDLE (Conditions Affecting Neurocognitive Development and Early Learning) pregnancy cohort in Memphis, Tennessee, with recruitment from 2006 to 2011, to equally represent male and female fetuses. Participants were 68% Black and 32% White. Hormones measured were maternal thyroid (thyrotropin [TSH] and free thyroxine [FT4]) and placental hormones (hCG, its hyperglycosylated form [hCG-h], and free α- [hCGα] and β-subunits [hCGβ]) in maternal serum (17-28 weeks). The primary outcome measurement was the Bayley Scales of Infant and Toddler Development. All forms of hCG were negatively associated with FT4 and not associated with TSH. hCGα was associated with cognitive development at age 1 year and jointly interacted with TSH to predict cognitive development at age 3 years. This pilot study added insight into the thyrotropic actions of hCG in the second trimester, and into the significance of this mechanism for brain development. More research is warranted to elucidate differences between hCGα, hCGβ, and hCG-h in relation to TH regulation and child brain function.