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Levothyroxine Treatment in Euthyroid Pregnant Women with Autoimmune Thyroid Disease: Effects on Obstetrical Complications

Department of Endocrinology (R.N., G.F.), Azienda Ospedaliera LE/1, 73100 Lecce, Italy; Department of Obstetrics and Gynecology (T.M.), Casa di Cura "Salus", 72100 Brindisi, Italy; Department of Internal Medicine (A.P., D.D.), Azienda Ospedaliera PR, "Di Vaio" Hospital, 43036 Fidenza, Italy; and Endocrine Unit (H.H.), Raja Isteri Pengiran Anak Saleha Hospital, Bandar Seri Begawan, Brunei Darussalam BA 1000

Address all correspondence and requests for reprints to: Roberto Negro, Department of Endocrinology, Azienda Ospedaliera LE/1, P.O. "V. Fazzi", Piazza F. Muratore, 73100 Lecce, Italy. E-mail: robnegro{at}tiscali.it.

Context: Euthyroid women with autoimmune thyroid disease show impairment of thyroid function during gestation and seem to suffer from a higher rate of obstetrical complications.

Objective: We sought to determine whether these women suffer from a higher rate of obstetrical complications and whether levothyroxine (LT₄) treatment exerts beneficial effects.

Design: This was a prospective study.

Setting: The study was conducted in the Department of Obstetrics and Gynecology.

Patients: A total of 984 pregnant women were studied from November 2002 to October 2004; 11.7% were thyroid peroxidase antibody positive (TPOAb⁺).

Intervention: TPOAb⁺ patients were divided into two groups: group A (n = 57) was treated with LT₄, and group B (n = 58) was not treated. The 869 TPOAb^– patients (group C) served as a normal population control group.

Main Outcome Measures: Rates of obstetrical complications in treated and untreated groups were measured.

Results: At baseline, TPOAb⁺ had higher TSH compared with TPOAb^–; TSH remained higher in group B compared with groups A and C throughout gestation. Free T₄ values were lower in group B than groups A and C after 30 wk and after parturition. Groups A and C showed a similar miscarriage rate (3.5 and 2.4%, respectively), which was lower than group B (13.8%) [P < 0.05; relative risk (RR), 1.72; 95% confidence interval (CI), 1.13–2.25; and P < 0.01; RR = 4.95; 95% CI = 2.59–9.48, respectively]. Group B displayed a 22.4% rate of premature deliveries, which was higher than group A (7%) (P < 0.05; RR = 1.66; 95% CI = 1.18–2.34) and group C (8.2%) (P < 0.01; RR = 12.18; 95% CI = 7.93–18.7).

Conclusions: Euthyroid pregnant women who are positive for TPOAb develop impaired thyroid function, which is associated with an increased risk of miscarriage and premature deliveries. Substitutive treatment with LT₄ is able to lower the chance of miscarriage and premature delivery.

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