Abstract

ObjectivesTo explore the effect of isolated maternal hypothyroxinemia (IMH) during the first and second trimester of gestation on pregnancy outcomes. To explore whether levothyroxine (L-T4) treatment of women who had IMH identified in the first trimester improves pregnancy outcomes.MethodsWomen in the early pregnancy in the iodine-sufficient area (n = 3398) were recruited to this prospective cohort study (ChiCTR-TRC-12002326). Serum thyroid-stimulating hormone (TSH), free thyroxine (FT4), and thyroid peroxidase antibody (TPOAb) were detected. Women with IMH before 12 weeks chose to receive L-T4 or remain untreated. The L-T4 dose was adjusted to attain a normal FT4 and TSH level. Pregnancy outcomes were evaluated during follow-up.ResultsIMH in the first trimester was not associated with increased risk of adverse pregnancy outcome compared with controls. The incidence of macrosomia (p = 0.022) and gestational hypertension (p = 0.018) was significantly higher in IMH identified in the second trimester of gestation compared with controls. IMH identified in the second trimester of gestation was a risk factor for macrosomia [adjusted odds ratio (aOR) 1.942, 95% CI 1.076–3.503, p = 0.027] and gestational hypertension (aOR 4.203, 95% CI 1.611–10.968, p < 0.01), when body mass index in the early pregnancy was < 25 kg/m2.ConclusionsIMH in the first trimester did not increase the risk of adverse outcomes irrespective of whether women received L-T4 treatment. However, IMH identified in the second trimester was associated with increased risk of adverse pregnancy outcome. The results suggest that thyroid function follow-up during the second trimester is necessary, even if thyroid function is normal during the first trimester.

Highlights

  • Thyroid hormones are crucial for a normal pregnancy and fetal development

  • By evaluating the thyroid function of pregnant women, we explored the effect of Isolated maternal hypothyroxinemia (IMH) in the first and second trimester of gestation on pregnancy outcomes and investigated whether levothyroxine (L-T4) intervention beginning before 12 gestational weeks could reduce IMH-related complications

  • Women identified with IMH during second trimester tended to be older (p = 0.024) and had a higher body mass index (BMI) (p < 0.01) in the early pregnancy compared with control

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Summary

Introduction

Thyroid hormones are crucial for a normal pregnancy and fetal development. Isolated maternal hypothyroxinemia (IMH) is defined as a low maternal free thyroxine (FT4) concentration in conjunction with a normal maternal thyroid-stimulating hormone (TSH) concentration. IMH during the early pregnancy is associated with the increased risk of placental abruption, gestational diabetes, macrosomia, and preterm delivery [2, 4, 5]. IMH in the second trimester of gestation may result in adverse pregnancy outcomes. The Generation R study in the Netherlands found that decreased maternal serum FT4 in the first half of pregnancy caused a 2.5- and 3.9-fold increased risk in premature and very premature delivery, respectively [7]. A review by Korevaar et al indicated that hypothyroxinemia may be associated with child neurocognitive development but not with adverse pregnancy outcomes [1]

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