Thyroid Function Rather Than Thyroid Antibodies Affects Pregnancy and Perinatal Outcomes

Results of a Prospective Study

Francesca Orsolini; Elena Gianetti; Chiara Terrenzio; Lucia Montanelli; Elena Benelli; Brunella Bagattini; Emilio Fiore; Massimo Tonacchera


J Clin Endocrinol Metab. 2022;107(11):e4302-e4310. 

In This Article

Abstract and Introduction


Context: Thyroid autoantibody positivity has been associated with an increased rate of obstetrical complications.

Objective: We aimed to evaluate the role of thyroid autoantibodies in adverse pregnancy outcomes.

Methods: This prospective study was conducted in the Endocrinology Unit of Pisa Hospital. A total of 975 pregnant women were studied from 2012 to 2021; 572 (59%) were diagnosed with autoimmune thyroid (AT) diseases; 403 (41%) served as controls. Levothyroxine (LT4) treatment was introduced when TSH was > 2.5 mIU/L in the AT group and when TSH was > 4 mIU/L in the controls. Rates of obstetrical complications in each group were measured.

Results: Although the frequency of miscarriage in the AT group was greater (4.8%) than in the controls (2.9%), no significant differences were detected (P = 0.181). There were no differences between the 2 groups concerning the other pregnancy complications, and no association with the titer of thyroid antibodies was observed. The frequency of congenital malformations was greater in the AT group than in the controls (P = 0.019), but no correlation with major congenital malformations was detected (P = 0.872). Given that thyroid hormone concentrations were strictly controlled in our population, we documented a tendency (not significant) toward an increase in miscarriage and preterm birth among women with TSH > 4 mIU/L.

Conclusion: If thyroid function is adequately controlled, the presence and titer of thyroid autoantibodies does not negatively influence gestation. Although not significant, suboptimal thyroid hormone status seems to affect pregnancy outcomes more than thyroid autoimmunity.


The presence of thyroid autoantibodies (anti-thyroglobulin thyroid autoantibodies, Tg-Ab, and anti-thyroperoxidase thyroid autoantibodies, TPO-Ab) is relatively common in women of reproductive age. Their estimated prevalence ranges from 2% to 17% in the pregnancy population[1–3] and varies with ethnicity.[4] Along with iatrogenic hypothyroidism, chronic autoimmune thyroiditis (AT) is the most common form of pregnancy-related hypothyroidism in countries with adequate iodine intake.[5] Dietary iodine deficiency remains the most common cause of hypothyroidism in developing countries. Conversely, hyperthyroidism in pregnancy affects 1 to 2 pregnancies/1000,[6] and autoimmune Graves disease (GD) is the most common cause (85%-90% of the cases). Overt maternal thyroid dysfunction has been clearly associated with adverse pregnancy outcomes as well as eclampsia, placental abruption, premature delivery, miscarriage, cesarean delivery, low birth weight, and fetal and neonatal neurocognitive impairment and congenital malformations.[7–10]

Furthermore, elevated anti-thyroid-stimulating hormone receptor antibody (TRAb) concentrations in autoimmune hyperthyroidism through placental transfer can directly affect fetal and neonatal thyroid function.[11] Several studies reported a positive correlation between the presence of thyroid autoantibodies and adverse pregnancy and perinatal outcomes, regardless of the thyroid dysfunction.[12–14] A metanalysis of literature described a 3-fold and a 2-fold risk of miscarriage and preterm birth, respectively, in women with thyroid autoimmunity compared with the control group.[14] Also, recurrent pregnancy loss and perinatal death seem to be more frequent in women with Tg-Ab and TPO-Ab positivity in some studies.[7,15,16] However, in the majority of the cases, perinatal death was due to preterm birth both in the group of women with autoantibody positivity and in the control group.[17] The increased rate of preterm delivery in women with autoimmune thyroid disease was partially attributable to a high prevalence of premature rupture of membranes.[14,18–21] Other studies confer to mild hypothyroidism the leading cause of the excess rate of miscarriage and preterm birth in women with autoimmune thyroiditis who have higher values of thyroid-stimulating hormone (TSH) in the first trimester of pregnancy and lower free thyroxine (FT4) values in the third trimester of pregnancy compared with healthy women.[22,23] Indeed, TPO-Ab–positive women have higher median TSH levels during pregnancy,[22,24] due to an impaired thyroidal response to physiological human chorionic gonadotropin (hCG) stimulation in early pregnancy, and a lower FT4 than expected for hCG. This reduction in thyroid functional capacity could lead to a suboptimal placental development and has been associated with a more than 2-fold higher risk of premature delivery compared with women with adequate thyroidal response to hCG.[25,26] Treatment with levothyroxine (LT4) reduced the number of pregnancy loss in euthyroid TPO-Ab–positive women in a study by Negro et al.[27] A few other studies correlated thyroid autoimmunity with different adverse pregnancy and neonatal outcomes as well as premature placental abruption, gestational diabetes, small for gestational age (SGA) condition,[17] low birth weight,[21] intrauterine growth restriction (IUGR)[28] and neonatal respiratory distress.[29] Anyway, the clinical significance of thyroid autoimmunity without thyroid dysfunction remains controversial. Therefore, we designed the present prospective study to elucidate the role of thyroid autoimmunity and maternal thyroid function on pregnancy outcomes.