Placental Angiogenic Factors Are Associated With Maternal Thyroid Function and Modify XXXX -Mediated FT4 Stimulation.

@entity1 @entity1375 @entity7309 @entity7 @entity3491 @entity3566 @entity4149
CONTEXT: The thyroid has a high vascular density and this vascularity may be influenced by pregnancy-specific angiogenic factors. Proangiogenic placental growth factor ( @entity7309 ) and antiangiogenic soluble FMS-like @entity4149 kinase-1 (sFlt1; a @entity7 [ @entity7 ] and @entity7309 antagonist) are important pregnancy-specific angiogenesis regulators. We previously showed that fetal levels of sFlt1 and @entity7309 are associated with newborn thyroid function. However, the maternal thyroid may also be affected as @entity7309 and @entity7 are secreted into the maternal circulation and cause a concomitant increase of sFlt1 to overcome adverse effects of angiogenesis overstimulation. DESIGN, SETTING, AND @entity1 : Maternal sFlt1, @entity7309 , TSH, FT4, or @entity1 chorionic gonadotropin ( @entity3566 ) levels were determined during early pregnancy (<18 wk) in 5517 @entity1 from the Generation R study. Analyses were adjusted for relevant covariates and interaction between @entity3566 and angiogenic factors was investigated. RESULTS: Increasing levels of sFlt1 were associated with a decrease in FT4 and T4 (both P < .001), and an increased risk of @entity1375 (odds ratio [OR] for high levels, 2.37; 95% CI, 1.16-4.83; P = .02) and @entity3491 (linear P = .02; OR, 3.05; 95% CI, 1.42-6.55; P = .004). Increasing levels of @entity7309 were associated with a decrease in TSH and FT4 levels (both P < .001), and an increased risk of @entity3491 (linear P = .002; OR, 1.77; 95% CI, 1.02-3.06; P = .04). High levels of @entity3566 decreased the difference in FT4 between low and high sFlt1. In @entity1 with high @entity7309 levels, the @entity3566 -mediated increase in FT4 levels was attenuated. CONCLUSION: sFlt1 and @entity7309 are novel determinants of maternal thyroid (dys)function during early pregnancy and the response of the maternal thyroid function to @entity3566 stimulation. These data provide novel insights into the pregnancy specific thyroid function physiology and suggest that high levels of pro- and anti-angiogenic factors may be a risk factor for adverse pregnancy outcomes via their effects on maternal thyroid function.
