The impact of isolated maternal hypothyroxinemia during the first and second trimester of gestation on pregnancy outcomes: an intervention and prospective cohort study in China

OBJECTIVES: To 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. METHODS: Women 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. RESULTS: IMH 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/m(2). CONCLUSIONS: IMH 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s40618-018-0960-7) contains supplementary material, which is available to authorized users.