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Endocrine Abstracts (2014) 34 OC1.3 | DOI: 10.1530/endoabs.34.OC1.3

Erasmus University Medical Center, Rotterdam, The Netherlands.


Introduction: Adequate thyroid hormone availability during early life is crucial for normal child growth and development. Fetal growth in utero heavily depends on angiogenesis. Placental growth factor (PlGF) is a proangiogenic factor sharing high homology with vascular endothelial growth factor (VEGF) whereas soluble FMS-like tyrosine kinase-1 (sFlt1) is a potent antagonist of VEGF and PlGF signaling. Since the thyroid is a highly vascularized organ, we hypothesized that fetal angiogenic factors influence in utero thyreogenesis and therefore investigated the effects of sFlt1 and PlGF on newborn thyroid (dys)function.

Methods: sFlt1, PlGF, TSH and free T4 were determined in cord blood of 3525 newborns from the Generation R Cohort. Analyses were adjusted for relevant maternal and child covariates.

Results: sFlt1 levels were positively associated with TSH (β (S.E.M.) +0.07 (0.02); P=0.0006) and inversely with FT4 (β (S.E.M.) −0.58 (0.11); P<0.0001). PlGF showed a positive association with FT4 (β (S.E.M.) +0.19 (0.02); P<0.0001). Elevated levels of sFlt1 were associated with a 3.2-fold increased risk of hypothyroxinemia (P=0.02). Decreased levels of PlGF were associated with a 7.3-fold increased risk of hypothyroxinemia (P<0.001). Within the normal range, a dose dependent effect of sFlt1 on thyroid dysfunction was observed: high-normal sFlt1 levels were associated with a 15.3-fold increased risk of hypothyroxinemia and a 2.9-fold increased risk of hyperthyrotropinemia (both P<0.0001).

Conclusion: Angiogenic factors sFlt1 and PlGF are novel determinants of newborn thyroid function. Most likely, this is mediated through effects on in utero thyreogenesis. Abnormal as well as normal-range sFlt1 and PlGF levels influence the risk of newborn thyroid dysfunction which has been associated with adverse neurodevelopmental effects. These data provide important novel insights into the physiology of thyreogenesis and into the etiology of newborn thyroid (dys)function.

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