Perinatal significance of isolated maternal hypothyroxinemia identified in the first half of pregnancy

OBJECTIVE: To establish pregnancy-specific free thyroxine thresholds and to assess perinatal effects associated with isolated maternal hypothyroxinemia identified in the first half of pregnancy. METHODS: Stored serum samples from 17,298 women who previously underwent thyroid-stimulating hormone (TSH) screening in the first half of pregnancy were analyzed for free thyroxine (T-4) concentrations and thyroid peroxidase antibodies. Women with a free T-4 below 0.86 ng/dL but a normal-range TSH were identified to have isolated maternal hypothyroxinemia. Pregnancy outcomes in these women were compared to those with a normal TSH and free T-4. Thyroid peroxidase antibody status and the relationship between TSH and free T-4 were analyzed for these women and women with subclinical hypothyroidism. RESULTS: Isolated maternal hypothyroxinemia was identified in 233 women (1.3%). There were not any excessive adverse pregnancy outcomes in these women. Positive thyroid peroxidase antibody assays (greater than 50 international units/mL) were similar in normal women (4%) and those with isolated hypothyroxinemia (5%) but were greater in women with subclinical hypothyroidism (31%, P<.001). There was a negative correlation between TSH and free T-4 in normal women (r(s)=-0.19, P<.001) and those with subclinical hypothyroidism (r(s)=-0.11, P=.007). The correlation in women with isolated hypothyroxinemia was not significant. CONCLUSION: Isolated maternal hypothyroxinemia has no adverse effects on perinatal outcome. Moreover, unlike subclinical hypothyroidism, there was a low prevalence of thyroid peroxidase antibodies and no correlation between TSH and free T-4 levels in women with hypothyroxinemia, leading us to question its biological significance.