Abstract

ObjectiveSubclinical 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 methodsWe 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 (FT4), free triiodothyronine (FT3), HbA1c, lipid profile, plasma glucose and insulin resistance (HOMA-IR) analysis) were obtained at 28 weeks gestation.ResultsIn comparison to euthyroid women (n=741), women with isolated hypothyroxinaemia (n=82) had significantly increased BMI (29.5 vs 27.5 kg/m2, 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 FT4 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 FT3:FT4 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.ConclusionsIsolated hypothyroxinaemia, but not subclinical hypothyroidism, is associated with adverse metabolic phenotype in pregnancy, as is decreasing maternal FT4 and increasing FT3:FT4 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.

Highlights

  • Increasing numbers of studies have shown associations between mild maternal thyroid hormone insufficiency in pregnancy and impaired neuropsychological development of the offspring, as well as several obstetric complications, such as miscarriage, preterm delivery, gestational hypertension and preeclampsia [1, 2, 3]

  • 174 : 1 and metabolic parameters gestational diabetes [7], and a recent study found that lower free thyroxine (FT4) levels and higher free triiodothyronine (FT3) to FT4 ratios in pregnant women are associated with several adverse metabolic parameters relating to obesity, glycaemia, insulin resistance and lipid profile [9]

  • In this study of healthy non-diabetic pregnant women, we found that women with isolated hypothyroxinaemia have worse metabolic parameters with increased obesity, glycaemia, triglycerides and insulin resistance compared to euthyroid women

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Summary

Introduction

Increasing numbers of studies have shown associations between mild maternal thyroid hormone insufficiency (including subclinical hypothyroidism and isolated hypothyroxinaemia) in pregnancy and impaired neuropsychological development of the offspring, as well as several obstetric complications, such as miscarriage, preterm delivery, gestational hypertension and preeclampsia [1, 2, 3]. Several of these studies [4, 5, 6], not all [7, 8] have shown that subclinical hypothyroidism in pregnancy is associated with an increased risk of gestational diabetes. As little is known on whether mild maternal thyroid hormone insufficiency in pregnancy is associated with adverse metabolic parameters, our study aimed to explore the relationship between maternal thyroid hormone levels and metabolic parameters in pregnancy and ascertain if pregnant women with subclinical hypothyroidism and isolated hypothyroxinaemia have worse metabolic phenotype than euthyroid pregnant women

Subjects and methods
Results
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