Maternal hypothyroxinaemia in pregnancy is associated with obesity and adverse maternal metabolic parameters

OBJECTIVE: Subclinical hypothyroidism and isolated hypothyroxinaemia in pregnancy have been associated with an increased risk of gestational diabetes. We aimed to ascertain if these women have a worse metabolic phenotype than euthyroid pregnant women. DESIGN, SUBJECTS AND METHODS: We recruited 956 healthy Caucasian women with singleton, non-diabetic pregnancies from routine antenatal clinics. Detailed anthropometric measurements (including BMI and skinfold thickness) and fasting blood samples (for TSH, free thyroxine (FT(4)), free triiodothyronine (FT(3)), HbA1c, lipid profile, plasma glucose and insulin resistance (HOMA-IR) analysis) were obtained at 28 weeks gestation. RESULTS: In comparison to euthyroid women (n=741), women with isolated hypothyroxinaemia (n=82) had significantly increased BMI (29.5 vs 27.5 kg/m(2), P<0.001), sum of skinfolds (57.5 vs 51.3 mm, P=0.002), fasting plasma glucose (4.5 vs 4.3 mmol/l, P=0.01), triglycerides (2.3 vs 2.0 mmol/l, P<0.001) and HOMA-IR (2.0 vs 1.3, P=0.001). Metabolic parameters in women with subclinical hypothyroidism (n=133) were similar to those in euthyroid women. Maternal FT(4) was negatively associated with BMI (r=−0.22), HbA1c (r=−0.14), triglycerides (r=−0.17), HOMA-IR (r=−0.15) but not total/HDL cholesterol ratio (r=−0.03). Maternal FT(3):FT(4) ratio was positively associated with BMI (r=0.4), HbA1c (r=0.21), triglycerides (r=0.2), HOMA–IR (r=0.33) and total/HDL cholesterol ratio (r=0.07). TSH was not associated with the metabolic parameters assessed. CONCLUSIONS: Isolated hypothyroxinaemia, but not subclinical hypothyroidism, is associated with adverse metabolic phenotype in pregnancy, as is decreasing maternal FT(4) and increasing FT(3):FT(4) ratio. These associations may be a reflection of changes in the thyroid hormone levels secondary to increase in BMI rather than changes in thyroid hormone levels affecting body weight and related metabolic parameters.