BACKGROUND
Thyroid hormone is essential for the development of the brain. In early pregnancy, the only source of thyroid hormone from the mother. If the mother has untreated hypothyroidism with an elevated TSH and low thyroid hormone (free T4) level, children may have lower IQ and developmental problems. Subclinical hypothyroidism is a milder form of hypothyroidism with an elevated TSH and normal thyroid hormone levels. The effect of this milder form of hypothyroidism on the child’s brain development is not as clear. There are other important unanswered questions about subclinical hypothyroidism, such as if treatment of the mother with thyroid hormone (levothyroxine) would make a difference, or how early in the pregnancy and at what TSH level should treatment start to make a difference. But the questions do not end there, as some mothers with hypothyroidism have antibodies against their thyroid while others do not. Thyroid peroxidase (TPO) antibodies are a marker of autoimmune thyroid disease, where the body makes antibodies that attack the thyroid. If the antibodies block or destroy the thyroid, the result is hypothyroidism. Indeed, autoimmune thyroid disease is the most common cause of hypothyroidism in the United States.

We do not have consistent information about whether having hypothyroidism or getting treatment with thyroid hormone during pregnancy would have the same effect if the TPO antibodies are absent. This study was designed to evaluate the brain development of children whose mothers had subclinical hypothyroidism without TPO antibodies (TPOAb-negative) and the impact of treatment with thyroid hormone (levothyroxine) in early pregnancy.

THE FULL ARTICLE TITLE
Chen J et al 2022 Subclinical hypothyroidism with negative for thyroid peroxidase antibodies in pregnancy: Intellectual development of offspring. Thyroid. Epub 2022 Jan 11. PMID: 34915770.

SUMMARY OF THE STUDY
The study was done at a university hospital in China. Researchers reviewed information from 2016 to 2019 retrospectively. They included information from women who were pregnant with a single baby and presented before the eighth week of pregnancy who had thyroid function tests and TPO antibodies measured. Mothers who had heart, liver, kidney disease or blood disorders were excluded.

Children were assigned to five different groups based on the mothers’ TSH levels and whether their mothers were treated with thyroid hormone. TPO antibodies were negative in all groups. Group A had TSH levels between 2.5 and 4 mIU/L, Group B had TSH levels 4 – 10 mIU/L. Groups A and B were treated with thyroid hormone (levothyroxine). Group C had TSH 2.5 – 4 mIU/L and Group D had TSH 4-10 mIU/L. Group C and D were not treated with levothyroxine. Group E had TSH levels less than 2.5 mIU/L (normal) and not treated with levothyroxine. This was the normal/control group. When the children reached 2 years of age, their development was evaluated by expert psychiatrists. Motor skills, language, adaptability and social skills were assessed and reported as a development quotient (DQ)

Ultimately, 139 children were included in the final analysis. A total of 112 had mothers with TPOAb-negative subclinical hypothyroidism and 27 mothers had normal thyroid tests. Group A (n=31), Group B (n=26), Group C (n=27), Group D (n=28), and Group E (n=27). Only Group D had a lower DQ compared to group E and the difference was similar in all areas of development. While there was no difference between groups A and C, the difference between groups B and D was significant. Another significant association was between the mother’s baseline TSH level and the DQ, when the TSH was higher the DQ was lower. The mother’s education and TSH levels were risk factors that affected the child’s intellectual development.

WHAT ARE THE IMPLICATIONS OF THIS STUDY?
The authors concluded that the brain development of children whose mothers had subclinical hypothyroidism without TPO antibodies during early pregnancy was related to the level of TSH. Children whose mothers had TSH levels above 4 mIU/L with negative TPO antibodies who were not treated, had problems with brain development. Thyroid hormone treatment before the eighth week of pregnancy significantly improved brain development.

The findings of this study support treating mild hypothyroidism in early pregnancy, but further research is needed. The screening and treatment approaches for mild hypothyroidism in early pregnancy would significantly change if these benefits are confirmed in larger studies.

— Ebru Sulanc, MD

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