Free T4, TSH receptor antibodies predict neonatal hypothyroidism in Graves’ disease
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Mothers who give birth to babies with neonatal hypothyroidism tend to have higher levels of free thyroxine and thyroid-stimulating hormone receptor antibodies than those whose newborns have normal thyroid levels, according to a study.
“This is the first study to identify risk factors throughout pregnancy that predicted neonatal hypothyroidism at delivery and to establish the cutoff antithyroid drug dose for risk of neonatal hypothyroidism, which varied with the maternal TSH receptor antibody levels in the third trimester,” Ai Yoshihara, MD, PhD, of the department of internal medicine at Ito Hospital in Tokyo, and colleagues wrote in Thyroid. “Since mothers who delivered infants with low free T4 levels or normal free T4 levels but extremely high TSH levels had high third trimester serum free T4 and TSH receptor antibody levels, they required high daily antithyroid drug doses, suggesting high maternal Graves’ disease activity.”
Researchers conducted a retrospective cohort study of 305 women with Graves’ disease who use antithyroid drugs and gave birth between Aug. 1, 2005, and May 5, 2022, at Ito Hospital. Data were collected from hospital medical records. Mothers were assessed every 4 to 8 weeks during the second and third trimester. Maternal thyroid hormone and umbilical cord blood levels were measured at delivery. Maternal free T4, TSH receptor antibodies and daily antithyroid drug doses were recorded at 20 to 28 weeks’ gestation, 28 to 36 weeks’ gestation and delivery.
Of the study cohort, 63 mothers used methimazole and 242 used propylthiouracil. Hypothyroidism was present in 19% of newborns from mothers using methimazole and 12.8% of newborns from mothers using propylthiouracil. There was no significant difference in neonatal hypothyroidism rates between the two groups.
Among women using methimazole, who delivered newborns with hypothyroidism were taking higher doses at 20 to 28 weeks of gestation (17.5 mg/day vs. 10 mg/day; P = .0019) and 28 to 36 weeks (15 mg/day vs. 5 mg/day; P = .0009) and had lower free T4 levels at delivery (0.93 ng/dL vs. 1.4 ng/dL; P = .0048) than those with euthyroid offspring. Women using propylthiouracil with hypothyroid offspring were also taking higher doses at 20 to 28 weeks of gestation (200 mg/day vs. 75 mg/day; P < .0001) and 28 to 36 weeks of gestation (200 mg/day vs. 50 mg/day; P < .0001) than mothers of euthyroid newborns. Among the propylthiouracil group, there were also higher TSH receptor antibody (6.1 IU/L vs. 3 IU/L; P = .019) and free T4 (1.48 ng/dL vs 1.12 ng/dL; P = .0011) levels among mothers of newborns with hypothyroidism vs. those with euthyroid offspring.
Each 5 mg increase in methimazole dose (OR = 1.941; 95% CI, 1.123-3.353) and each 50 mg increase in propylthiouracil dose (OR = 2.307; 95% CI, 1.713-3.107) at 28 to 36 weeks of gestation was associated with increased odds for neonatal hypothyroidism. The cutoff dose predicting neonatal hypothyroidism was 10 mg per day for methimazole users and 150 mg per day for propylthiouracil users.
“The cutoff methimazole dose was 10 mg per day but increased to 20 mg per day when the maternal TSH receptor antibody value in the third trimester was above three times the upper limit of the normal reference range,” the researchers wrote. “The cutoff propylthiouracil dose for predicting neonatal hypothyroidism was 150 mg per day and did not vary with the TSH receptor antibody value. Careful follow-up is necessary when maternal Graves’ disease remains active and the antithyroid drug dose required to control maternal thyrotoxicosis cannot be reduced.”
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