Objective: Gestational thyroid dysfunction and gestational diabetes mellitus (GDM) are common complications during pregnancy and often co-occur. Since thyroid hormones increase glucose uptake and insulin sensitivity, our aim was to study if maternal thyroid function test abnormalities are risk factors for GDM.

Methods: We performed a systematic search for prospective cohort studies and issued open invitations to authors to participate in the current study. The primary outcome was GDM. Individual-participant data were analyzed using logistic mixed-effects regression models adjusting for maternal age, BMI, smoking, parity, ethnicity, and gestational age at blood sampling. Sensitivity analyses included cohorts which performed universal screening.

Results: From 468 published articles, 36 cohorts were invited and 21 cohorts were included after agreeing to participate, including 64370 participants after exclusions. There were 1789 (2.8%, range 0.5-12.9%) cases of GDM, 239 (0.4%) had overt hypothyroidism, 1896 (3.3%) had subclinical hypothyroidism and 1299 (2.3%) had isolated hypothyroxinemia. Isolated hypothyroxinemia was associated with a higher risk of GDM as compared to euthyroid women [absolute risk 3.2% vs 2.3%, respectively; Odds Ratio (OR), 1.56; CI, 1.21-2.01; p=0.001]. In the continuous analyses, each 1 SD decrease of free thyroxine (FT4) was associated with an increased risk of GDM [OR, 1.14; 95% CI, 1.08-1.18; p<0.001]. In the universal screening only analysis, including 8 cohorts 15702 participants and 1020 cases of GDM, with similar results were found [OR, 1.14; 95% CI, 1.05-1.22; p=0.001]. For thyroid stimulating hormone and other disease entities no significant association was found.

Conclusions: Among pregnant women, both isolated hypothyroxinemia and relatively low FT4 concentrations were significantly associated with a higher risk of GDM. These findings hold particular significance for pregnant individuals undergoing treatment with either insulin or levothyroxine, as the effects of these therapies may fluctuate throughout the gestational period.