The association of thyroid function with maternal and neonatal homocysteine concentrations

Abstract

Context: High homocysteine concentrations are associated with maternal pregnancy complications and low birth weight, jaundice, and cerebrovascular accidents in neonates. Thyroid hormone may interfere with homocysteine metabolism via stimulation of vitamin B12- and folate-dependent processes and via effects on enzymes of the remethylation pathway. Objective: Investigating the associations of maternal and neonatal thyroid function with homocysteine during pregnancy and after delivery, respectively. Design, Setting, and Participants: Within Generation R study, a population-based prospective cohort, we studied the associations of maternal and neonatal thyroid stimulating hormone (TSH) and free thyroxine (FT4) with homocysteine, folate, and vitamin B12 concentrations using multiple linear regression analyses. Main Outcome Measures: TSH, FT4, homocysteine, folate, and vitamin B12 concentrations were determined in early pregnancy (,18 weeks; N = 1094 women without folic acid supplementation) and in cord blood of 4475 neonates. Results: In neonates, there was a positive association of FT4 with homocysteine and an inverse association of TSH with homocysteine. The associations attenuated after adjustment for folate and vitamin B12 concentration (b change: for FT4, 0.0055960.001, P,0.0001, to 0.0031060.001, P = 0.015; and for TSH, -0.0016560.001, P = 0.005, to -0.0008660.001, P = 0.11). Inmothers, therewas a positive association of FT4 with homocysteine (P = 0.026) but no association of FT4 with folate or vitamin B12 (P $ 0.08). Conclusion: Higher thyroid function is associated with higher homocysteine concentrations in pregnant women and in neonates. These data provide new insights into the effects of thyroid hormone on folate- and vitamin B12-dependent processes during early growth and development.