Thyroid antibody positivity in the first trimester of pregnancy is associated with negative pregnancy outcomes.

CONTEXT: Thyroid antibody positivity during pregnancy has been associated with adverse outcomes including spontaneous miscarriage, recurrent miscarriage, and preterm delivery. OBJECTIVE: The objective of the study was to determine whether thyroid antibody positivity in the first trimester of pregnancy in euthyroid women was associated with maternal and neonatal adverse outcomes. DESIGN: The present trial is a component of a prospective trial published in 2010 that evaluated screening for thyroid disease during pregnancy and the impact of levothyroxine therapy in women who were thyroid peroxidase positive with a TSH above 2.5 mIU/liter. The present study compared 14 maternal and neonatal adverse outcomes in 245 women who were euthyroid (TSH < 2.5 mIU/liter) and thyroid peroxidase positive in the first trimester to 3348 women who were euthyroid and thyroid peroxidase negative in the first trimester. SETTING: The study was conducted in southern Italy at the ambulatory clinics of two community hospitals. PATIENTS: The study consisted of 3593 women. INTERVENTION: There was no intervention. MAIN OUTCOME MEASURES: The main outcome measures were 14 maternal and neonatal complications. RESULTS: The main result was an increase in very preterm delivery (<34 wk gestation at delivery) [4.5 vs. 1.8%; χ(2)(df = 1) = 8.58; P = 0.003] and respiratory distress [3.3 vs. 1.2%; χ(2)(df = 1) = 7.80; P = 0.005] in women who were thyroid antibody positive. CONCLUSIONS: The present study provides further evidence of an association between thyroid antibody positivity and very preterm delivery in euthyroid women. The association with respiratory distress should be considered preliminary and awaits further study.

High rate of persistent hypothyroidism in a large-scale prospective study of postpartum thyroiditis in southern Italy.

CONTEXT: The incidence of postpartum thyroiditis (PPT) varies widely in the literature. Limited data exist concerning the hormonal status of women with PPT at the end of the first postpartum year. OBJECTIVE: Our aim was to conduct a large prospective study of the incidence and clinical course of PPT. DESIGN: A total of 4394 women were screened for thyroid function and thyroid autoantibodies at 6 and 12 months postpartum. Women were classified as being at high or low risk of having thyroid disease before any thyroid testing. SETTING: The study was conducted at two ambulatory clinics in southern Italy, an area of mild iodine deficiency. PATIENTS: A total of 4394 pregnant women were studied. INTERVENTION: There was no intervention. MAIN OUTCOME MEASURES: We measured incidence, clinical presentation, and course of postpartum thyroiditis. RESULTS: The incidence of postpartum thyroiditis was 3.9% (169 of 4384). Women classified as being at high risk for thyroid disease had a higher incidence of PPT than women classified as low risk (11.1 vs. 1.9%; odds ratio, 6.69; 95% confidence interval, 4.63, 9.68). Eighty-two percent of the 169 women with PPT had a hypothyroid phase during the first postpartum year. At the end of the first postpartum year, 54% of the 169 women had persistent hypothyroidism. CONCLUSIONS: One of every 25 women in southern Italy developed PPT. Women at high risk for thyroid disease have an increased rate of PPT. The high rate of permanent hypothyroidism at 1 yr should result in a reevaluation of the widely held belief that most women with PPT are euthyroid at the end of the first postpartum year.

Increased pregnancy loss rate in thyroid antibody negative women with TSH levels between 2.5 and 5.0 in the first trimester of pregnancy.

CONTEXT: The definition of what constitutes a normal TSH during pregnancy is in flux. Recent studies suggested that the first trimester upper limit of normal for TSH should be 2.5 mIU/liter. OBJECTIVE: The objective of the study was to evaluate the pregnancy loss and preterm delivery rate in first-trimester thyroid peroxidase antibody-negative women with TSH values between 2.5 and 5.0 mIU/liter. DESIGN: The present study is a component of a recently published large-scale prospective trial that evaluated the impact of levothyroxine treatment on maternal and neonatal complications in thyroid peroxidase-positive women with TSH levels above 2.5 mIU/liter. The present study evaluated 4123 thyroid peroxidase antibody-negative women with TSH levels at or below 5.0 mIU/liter. Women were divided into two groups based on their initial TSH: group A, TSH level below 2.5 mIU/liter, excluding hyperthyroid women defined as an undetectable TSH with an elevated free T(4), and group B, TSH level between 2.5 and 5.0 mIU/liter. SETTING: The study was conducted at two ambulatory clinics of community hospitals in southern Italy. PATIENTS: A total of 4123 women were evaluated. INTERVENTION: There was no intervention. MAIN OUTCOME MEASURES: The incidence of pregnancy loss and preterm delivery in group A as compared with group B was measured. RESULTS: The rate of pregnancy loss was significantly higher in group B as compared with group A (6.1 vs. 3.6% respectively, P = 0.006). There was no difference in the rate of preterm delivery between the two groups. CONCLUSIONS: The increased incidence of pregnancy loss in pregnant women with TSH levels between 2.5 and 5.0 mIU/liter provides strong physiological evidence to support redefining the TSH upper limit of normal in the first trimester to 2.5 mIU/liter.

Universal screening versus case finding for detection and treatment of thyroid hormonal dysfunction during pregnancy.

CONTEXT: Thyroid disease during pregnancy has been associated with multiple adverse outcomes. Whether all women should be screened for thyroid disease during pregnancy is controversial. OBJECTIVE: The objective of the study was to determine whether treatment of thyroid disease during pregnancy decreases the incidence of adverse outcomes and compare the ability of universal screening vs. case finding in detecting thyroid dysfunction. DESIGN: Women in the first trimester were randomly assigned to the universal screening group or case-finding group. Women in both groups were stratified as high risk or low risk based on risk factors for thyroid disease. All women in the universal screening group, and high-risk women in the case-finding group, were immediately tested for free T(4), TSH, and thyroid peroxidase antibody. Low-risk women in the case-finding group had their sera tested postpartum. SETTING: The study was conducted at two ambulatory clinics of community hospitals in southern Italy. PATIENTS: A total of 4562 women were randomly assigned to the universal screening or case-finding group. INTERVENTION: Intervention included levothyroxine in women with a TSH above 2.5 mIU/liter in TPO antibody-positive women and antithyroid medication in women with a undetectable TSH and elevated free T(4). MAIN OUTCOME MEASURE: Total number of adverse obstetrical and neonatal outcomes was measured. RESULTS: No significant differences were seen in adverse outcomes between the case-finding and universal screening groups. Adverse outcomes were less likely to occur among low-risk women in the screening group than those in the case-finding group. CONCLUSIONS: Universal screening compared with case finding did not result in a decrease in adverse outcomes. Treatment of hypothyroidism or hyperthyroidism identified by screening a low-risk group was associated with a lower rate of adverse outcomes.

Levothyroxine treatment in thyroid peroxidase antibody-positive women undergoing assisted reproduction technologies: a prospective study.

BACKGROUND: Infertile women positive for thyroid antibodies suffer from a poor pregnancy/delivery outcome, although conflicting data have been published. Our objective was to investigate if levothyroxine (LT4) exerts any effect on pregnancy and/or delivery rates in thyroid peroxidase antibody (TPOAb)-positive (+) women undergoing assisted reproductive technologies. METHODS: Patients undergoing treatment were screened for TPOAb, thyroid-stimulating hormone (TSH) and free thyroxine (FT4). A total of 72 (15%) out of the 484 euthyroid women selected were TPOAb (+). These 72 patients were randomly divided into two groups: group A (n = 36) underwent LT4 treatment, group B (n = 36) placebo. Group C consisted of 412 women (85%) who were TPOAb negative (-). All patients received controlled ovarian stimulation. The endpoints of treatment were pregnancy rate, miscarriage rate and delivery rate. RESULTS: No differences in pregnancy rate were observed between the three groups. Miscarriage rate was higher in TPOAb (+) in comparison to TPOAb (-) [relative risk: 2.01 (95% CI = 1.13-3.56), P = 0.028]. CONCLUSIONS: The pregnancy rate is not affected either by presence of TPOAb or treatment with LT4. However, TPOAb (+) women show a poorer delivery rate compared to TPOAb (-). LT4 treatment in TPOAb (+) does not affect the delivery rate.