Evaluating the Progression to Hypothyroidism in Preconception Euthyroid Thyroid Peroxidase Antibody–Positive Women

Abstract

Abstract Context Thyroid peroxidase antibody (TPOAb) positivity is prevalent in women of reproductive age and predisposes to thyroid dysfunction, particularly hypothyroidism, which has adverse effects on pregnancy. Objective This study aimed to report the rate of development of abnormal thyroid function among initially euthyroid TPOAb-positive women recruited into the TABLET trial, to identify factors associated with the development of hypothyroidism, and to compare outcomes between euthyroid and treated hypothyroid individuals. Methods This observational cohort study, conducted at 49 UK hospitals between 2011 and 2016, included euthyroid TPOAb-positive women 16 to 40 years of age with a history of miscarriage or subfertility, planning pregnancy, randomized to levothyroxine 50 mcg daily or placebo. Abnormal thyroid function, conception rate, and live birth rate (LBR) ≥34 weeks were analyzed. Results Among the women, 70/940 (7.4%) developed subclinical (SCH) or overt (OH) hypothyroidism: 27/470 taking levothyroxine and 43/470 placebo (relative risk [RR] 0.63; 95% CI, 0.39-1.00; P = 0.05); 83% of cases emerged prepregnancy. Baseline median serum TSH concentrations and TPOAb titers were significantly higher in those who developed hypothyroidism vs those who did not (P < 0.001). Treated SCH/OH demonstrated a higher failure-to-conceive rate compared with euthyroid women (adjusted RR 2.02 [1.56-2.62]; P < 0.001). The LBR ≥ 34 weeks was similar in the treated SCH/OH and euthyroid groups (adjusted RR 1.09 [0.77-1.55]; P = 0.6). Conclusion Approximately 7% of euthyroid TPOAb-positive women will develop hypothyroidism within 1 year preconception or in pregnancy. Conception rates are lower in women with treated SCH/OH compared with euthyroid women, but LBR are comparable. Thyroid function in TPOAb-positive women should be monitored regularly, when trying to conceive, to ensure prompt diagnosis and appropriate treatment initiation.