Placental angiogenic factors are associated with maternal thyroid function and modify HCG-mediated FT4 stimulation

Abstract

Context: The thyroid has a high vascular density and this vascularity may be influenced by pregnancy-specific angiogenic factors. Proangiogenic placental growth factor (PlGF) and antiangiogenic soluble FMS-like tyrosine kinase-1 (sFlt1; a vascular endothelialgrowthfactor [VEGF]andPlGF antagonist) are important pregnancy-specific angiogenesis regulators.Wepreviously showed that fetal levels of sFlt1 and PlGF are associated with newborn thyroid function. However, the maternal thyroid may also be affected as PlGF and VEGF are secreted into the maternal circulation and cause a concomitant increase of sFlt1 to overcome adverse effects of angiogenesis overstimulation. Design, Setting, and Participants: Maternal sFlt1, PlGF, TSH, FT4, or human chorionic gonadotropin (hCG) levels were determined during early pregnancy (∼18 wk) in 5517 women from the Generation R study. Analyses were adjusted for relevant covariates and interaction between hCG and angiogenic factors was investigated. Results: Increasing levels of sFlt1 were associated with a decrease in FT4 and T4 (both P < .004). Increasing levels of PlGF were associated with a decrease in TSH and FT4 levels (both < .002; OR, 1.77; 95% CI, 1.02-3.06;