Hyperthyroidism and Birth Defects: The Roles of Maternal Thyroid Function and Thyroid Autoantibody Positivity

CONTEXT: An increased risk of birth defects in children born to mothers with hyperthyroidism has been found, and uncertainties prevail on the role of maternal thyroid function and thyroid autoimmunity. OBJECTIVE: To evaluate the association between maternal thyroid function, thyroid autoantibodies, and birth defects. METHODS: Retrospective cohort study of 20 399 pregnant women with no known thyroid disease and their children from the Danish National Birth Cohort and the North Denmark Region Pregnancy Cohort. Blood samples from early pregnancy (median week 10) were assessed for maternal TSH and free T4 in both cohorts and for thyroid peroxidase antibodies and thyroglobulin antibodies as well as TSH receptor antibodies and thyroid stimulating immunoglobulin in the North Denmark Region Pregnancy Cohort. Information on birth defects was retrieved from hospital diagnoses. RESULTS: Altogether 702 children (3.4%) had birth defects, and maternal median TSH (no birth defects: 1.13 mIU/L; birth defects: 1.19 mIU/L; P = .1) and free T4 (no birth defects: 15.5 pmol/L; birth defects: 15.7 pmol/L; P = .3) did not differ by outcome of birth defect. The prevalence of birth defects was similar in children born to mothers who were thyroid peroxidase antibodies- or thyroglobulin antibodies-positive (4.3%) or negative (4.0%; P = .6) but higher (9.5%) when the mother was positive for TSH receptor antibodies or thyroid stimulating immunoglobulin (P = .003). CONCLUSION: In a large Danish pregnancy cohort, no evidence was found that maternal thyroid function in early pregnancy is associated with a risk of birth defects. A possible link with maternal thyroid stimulating antibodies warrants further investigation.