Maternal Thyroid Hormone Levels in Early Pregnancy Not Tied to Birth Defects: Study
Denmark: Maternal thyroid hormone levels in early pregnancy may not increase the risk of birth defects in children, a large cohort study from Denmark has revealed. However, the presence of thyroid-stimulating autoantibodies in pregnant women may be linked to a higher risk of congenital anomalies. The findings were published in The Journal of Clinical Endocrinology & Metabolism by Stine Linding Andersen of Aalborg University Hospital, Denmark, and colleagues.
Hyperthyroidism during pregnancy, particularly in women with Graves’ disease, has been associated with adverse fetal outcomes. However, it has remained unclear whether maternal thyroid hormone levels or thyroid-related autoimmunity contribute to the risk of birth defects. The current study aimed to clarify these associations by examining maternal thyroid function and autoantibody status during early pregnancy.
Researchers conducted a retrospective cohort study involving 20,399 pregnant women with no known thyroid disease and their singleton live-born children. Data were obtained from the Danish National Birth Cohort and the North Denmark Region Pregnancy Cohort, using information from national health registries.
Blood samples collected in early pregnancy, at a median gestational age of around 10 weeks, were used to assess maternal thyroid status. The researchers measured thyroid-stimulating hormone (TSH) and free thyroxine (fT4) levels to evaluate thyroid function. They also examined several thyroid autoantibodies, including thyroid peroxidase antibodies (TPO-Abs), thyroglobulin antibodies (Tg-Abs), TSH receptor antibodies (TRAbs), and thyroid-stimulating immunoglobulin (TSI). Maternal thyroid function was classified according to whether TSH levels fell within or outside the cohort-specific reference range.
Information on birth defects was obtained from hospital diagnoses recorded in national registries, with outcomes tracked until children reached two years of age.
The study led to the following findings:
- Overall, 702 children (3.4%) were diagnosed with birth defects.
- Maternal TSH and free T4 (fT4) levels were similar in mothers of children with birth defects and those whose children had no congenital anomalies.
- Maternal thyroid hormone levels in early pregnancy were not associated with an increased risk of birth defects.
- The prevalence of congenital anomalies was comparable among children born to mothers who were positive or negative for thyroid peroxidase antibodies (TPO-Abs) and thyroglobulin antibodies (Tg-Abs).
- A higher prevalence of birth defects was observed in children born to mothers who tested positive for TSH receptor antibodies (TRAbs) or thyroid-stimulating immunoglobulin (TSI).
- Exposure to maternal TRAbs and/or TSI was associated with a 3.5-fold higher risk of birth defects.
- Among seven children with birth defects exposed to maternal TSI, four had cardiac malformations.
The researchers noted that while maternal thyroid hormone levels in early pregnancy do not appear to increase the risk of birth defects, thyroid-stimulating antibodies may play a role and warrant further investigation. They added that these findings may help guide clinical management and treatment considerations for hyperthyroidism, particularly Graves’ disease, during pregnancy.
Reference:
Andersen, S. L., Torp, N. M., Vestergaard, P., & Andersen, S. Hyperthyroidism and Birth Defects: The Roles of Maternal Thyroid Function and Thyroid Autoantibody Positivity. The Journal of Clinical Endocrinology & Metabolism. https://doi.org/10.1210/clinem/dgag046
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