Endocrine Abstracts

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, it has been hypothesized that hypothyroidism might increase the risk of GDM. Our aim was to study if maternal thyroid function test abnormalities are risk factors for GDM.

Methods: A systematic search of Ovid MEDLINE, EMBASE and Web of Science was performed by two reviewers independently from inception to October 12, 2022 for prospective cohort studies with data on maternal thyroid function and GDM. We issued open invitations to authors to participate in the current study. We excluded participants who used assisted reproductive technology, had pre-existing thyroid disease, multiple pregnancies or were taking medications that affect thyroid function. 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. The study protocol was registered with PROSPERO CRD42022371927. Since screening methods (universal or selective) differed considerably between cohorts, sensitivity analyses including only cohorts which performed universal screening were done.

Results: From 468 published articles, 36 cohorts were invited and 21 cohorts were included after agreeing to participate. After exclusions, 64370 participants were included in the analyses. Of participants with complete data, 239 (0.4%) had overt hypothyroidism, 1896 (3.3%) had subclinical hypothyroidism, 1299 (2.3%) had isolated hypothyroxinemia, 850 (1.5%) had subclinical hyperthyroidism and 533 (0.9%) had overt hyperthyroidism. There were 1789 (2.8%, range 0.5-12.9%) cases of GDM in all cohorts. In the subset with universal screening, including 8 cohorts with 15702 participants, 1020 women had GDM (6.5%, range 1.6-12.9%). 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 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 add to the existing evidence on the risk of adverse events in women with gestational thyroid dysfunction and could inform the decision on targeted screening programs for GDM.