Free thyroxine in early pregnancy is an independent negative predictor of 3rd trimester HbA1c. Odense child cohort

Clin Endocrinol (Oxf). 2021 Sep;95(3):508-519. doi: 10.1111/cen.14492. Epub 2021 Jun 11.


Background: Lower thyroid function outside pregnancy is associated with an increased risk of type 2 diabetes mellitus. The relationship between thyroid function in early pregnancy and glucose status in 3rd trimester has not been investigated.

Aims: To study the association between 1st trimester thyroid function and 3rd trimester glucose status.

Design: In the prospective study Odense Child Cohort (OCC), 1,041 women had 1st trimester blood samples analysed for thyroid-stimulating hormone (TSH), free T4 (FT4), thyroid peroxidase antibody and HbA1c. Third trimester (week 28) fasting blood samples included plasma glucose, insulin and HbA1c. Oral glucose tolerance test (OGTT, 75 g glucose) was performed in 509 women. First trimester FT4 was dichotomized >vs. ≤ the 25th percentile (25p = 12.9 pmol/L). Homeostatic model assessment-insulin resistance (HOMA)-IR and HOMA-β were calculated.

Results: Women with FT4 ≤25p had significantly higher HbA1c in 1st and 3rd trimesters and higher 3rd trimester fasting glucose, insulin, HOMA-IR and HOMA-β compared to women with FT4 >25p. In multiple regression analyses, FT4 was an independent negative predictor of 3rd trimester HbA1c. FT4 levels in 3rd and 4th quartiles (high-normal FT4 levels) showed closest inverse associations with HbA1c (p-trend <.001). TSH was not associated with 3rd trimester HbA1c.

Conclusion: Women with lower levels of FT4 in early pregnancy had higher HbA1c in 3rd trimester and FT4 was an independent negative predictor of 3rd trimester HbA1c.

Keywords: FT4; HbA1c; glucose; insulin; pregnancy.

MeSH terms

  • Child
  • Diabetes Mellitus, Type 2*
  • Female
  • Glycated Hemoglobin A
  • Humans
  • Pregnancy
  • Pregnancy Trimester, Third
  • Prospective Studies
  • Thyroxine*


  • Glycated Hemoglobin A
  • Thyroxine