Negro, R., Formoso, G., Mangieri, T., Pezzarossa, A., Dazzi, D., & Hassan, H. (2006). Levothyroxine treatment in euthyroid pregnant women with autoimmune thyroid disease: effects on obstetrical complications. The Journal of Clinical Endocrinology and Metabolism, 91(7), 2587-2591. https://doi.org/10.1210/jc.2005-1603
Negro R, Formoso G, Mangieri T, Pezzarossa A, Dazzi D, Hassan H. Levothyroxine treatment in euthyroid pregnant women with autoimmune thyroid disease: effects on obstetrical complications. J Clin Endocrinol Metab. 2006;91(7):2587-2591. doi:10.1210/jc.2005-1603
Negro, Roberto, et al. "Levothyroxine treatment in euthyroid pregnant women with autoimmune thyroid disease: effects on obstetrical complications." The Journal of Clinical Endocrinology and Metabolism, vol. 91, no. 7, 2006, pp. 2587-2591.
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Raja Isteri Pengiran Anak Saleha Hospital010wh8q62
Department of Endocrinology (R.N., G.F.), Azienda Ospedaliera LE/1, 73100 Lecce, Italy
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RRM Academy Synopsis
Levothyroxine lowered miscarriage in pregnant antibody-positive women
Women with thyroid antibodies who took levothyroxine in pregnancy miscarried less often than untreated women. This prospective Italian study followed 115 antibody-positive women with normal thyroid function. About 4 out of 100 treated women miscarried, against about 14 out of 100 untreated. Preterm births showed the same pattern, about 7 out of 100 against about 22 out of 100.
Miscarriage, antibody-positive women: Antibodies, levothyroxine, 3.5 in 100; Antibodies, no treatment, 13.8 in 100. Source: Negro R et al., 2006, PMID 16621910.Study at a glance, prospective Italian study of 115 antibody-positive women: Levothyroxine lowered miscarriage in pregnant antibody-positive women. Source: Negro R et al., 2006, PMID 16621910.
Key Findings
Of 984 women, 11.7% were thyroid peroxidase antibody (TPOAb) positive. Of these, 57 received levothyroxine, 58 did not, and 869 antibody-negative women served as a normal control group.
Miscarriage occurred in 3.5% of treated antibody-positive women, 13.8% of untreated antibody-positive women and 2.4% of antibody-negative women.
Preterm delivery occurred in 7% of treated antibody-positive women, 22.4% of untreated antibody-positive women and 8.2% of antibody-negative women.
Later in pregnancy, thyroid-stimulating hormone was higher and free T4 was lower in untreated antibody-positive women than in treated women and antibody-negative women.
Rates of hypertension, preeclampsia and placental abruption did not vary between the groups, and neither did newborn weight, height, head size or APGAR score.
Interpretation
The study followed women forward in time. Researchers randomly assigned the 115 antibody-positive women to levothyroxine, a thyroid hormone, or to no treatment. The two groups held 57 and 58 women, with an average age of 30 years in each. The study took place in Italy, a country the authors describe as iodine deficient. Women with overt hypothyroidism, hyperthyroidism or preexisting thyroid dysfunction were excluded, and the participants were Caucasian. The authors note that the higher miscarriage rate in antibody-positive women may be partly due to age, since they were about 2 years older than antibody-negative women.
RRM Context
Thyroid autoimmunity is a measurable condition. A cause-based evaluation can identify it in a pregnancy at risk of loss or preterm birth. The authors agree with a 2003 recommendation to screen women early in pregnancy for thyroid antibodies and thyroid function. Restorative reproductive medicine puts evaluation before treatment: clinicians look for the cause of a loss and match the response to the finding.
Our editorial summary of this paper, not the article's abstract.
Abstract
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 (LT(4)) 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 LT(4), 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 T(4) 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 LT(4) is able to lower the chance of miscarriage and premature delivery.
