An Alternate Approach to Neonatal Screening of Thyroid Function

Background: Thyroid hormone (TH) plays a critical role in early fetal brain development during the first trimester, including the proliferation, migration, and differentiation of neuronal cells. Because this developmental window occurs before birth, some neurological defects may be irreversible by the time treatment begins after birth according to the current neonatal screening. There are persistent reports of mild brain damage and lower IQ in some children with congenital hypothyroidism (CH), despite early detection and treatment after birth, reveal potential shortcomings in the current neonatal screening strategy and underscore the need for improvement. Methods: In this report we propose an alternate approach to assess fetal thyroid function in utero by examining the characteristic fetal thyroid hormone (TH) metabolism —specifically, the sulfation pathway. Results: Sulfoconjugation is a major metabolic pathway for TH in developing mammals due to low type 1 monodeiodinase. The significant rise of sulfated iodothyronines in mammalian fetal compartments raises the possibility that significant fetal to maternal transfer of the conjugates may occur in late gestation as the fetal hypothalamic-pituitary-thyroid system become more mature. This transfer may be a novel mechanism to maintain low T3 states or regulate serum T2, a thermogenic hormone that is important for normal tissue maturity. The possibility that the transferred iodothyronine sulfate, especially T2S and its metabolite may serve as a marker of fetal thyroid function needs to be further explored. Conclusions: Further investigation into fetal TH metabolism and function may provide a rational alternative for managing CH at the early stage of fetal development and mitigating long-term adverse outcomes from neonatal-screen-associated “catch-up” treatment postnatally.