Iron Deficiency May Predict Greater Risk for Hypothyroxinemia: A Retrospective Cohort Study of Pregnant Women in China

Background: Pregnant women are highly vulnerable to iron deficiency (ID) due to the increased iron needs during pregnancy. ID decreases circulating thyroid hormone concentrations likely through impairment of iron-dependent thyroid peroxidase. The present study aimed to explore the association between ID and hypothyroxinemia in a retrospective cohort of pregnant women in China. Methods: To investigate the relationship between ID and hypothyroxinemia, 723 pregnant women were retrospectively analyzed, including 675 and 309 women in the second and third trimesters, respectively. Trimester-specific hypothyroxinemia was defined as free thyroxine (fT4) levels below the 2.5th percentile of the reference range with normal serum thyrotropin (TSH) or TSH higher than the 97.5th percentile of the reference range in each trimester of pregnancy. Serum TSH, fT4, thyroid peroxidase antibodies, thyroglobulin antibodies, serum ferritin, soluble transferrin receptor, and urinary iodine concentrations were measured. Serum ferritin, soluble transferrin receptor, and total body iron were used to indicate the nutritional iron status. Results: Cross-sectional multiple linear regression analysis showed that iron status was positively associated with serum fT4 levels in the first and second trimesters of pregnancy, but not in the third trimester. Logistic regression analysis showed that ID was an independent risk factor for hypothyroxinemia (odds ratio=14.86 [confidence interval 2.31-95.81], p=0.005 in the first trimester and odds ratio=3.36 [confidence interval 1.01-11.21], p=0.048 in the second trimester). The prospective analysis showed that pregnant women with ID during the first trimester of pregnancy had lower serum fT4 levels and a higher rate of hypothyroxinemia in the second or third trimester than those without ID. Conclusions: ID appears to be a risk factor to predict hypothyroxinemia in the first and second trimesters of pregnancy, but not in the third trimester. Pregnant women with ID in the first and second trimesters should be regarded as a high-risk group for maternal hypothyroxinemia.