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Low Serum IL-17A in Pregnancy During Second Trimester Is Associated With an Increased Risk of Subclinical Hypothyroidism.

ABSTRACT: Problem: Interleukin-17A (IL-17A) has a role in sustaining normal pregnancy. IL-17A is also associated with thyroid autoimmunity during pregnancy. This study sought to investigate whether IL-17A is a risk factor for thyroid dysfunction during pregnancy in women negative for thyroid autoantibodies. Methods of Study: The study comprised 216 pregnant women with negative thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TGAb) during the second trimester who provided blood samples for serum IL-17A, thyroid autoantibodies and thyroid function tests. To further evaluate the ratio of CD4+IL-17A+ Th17 cells, we collected peripheral blood from 26 women with thyroid-stimulating hormone (TSH) levels ≤ 2.5 mIU/L and 26 pregnancy-week matched women with TSH levels >2.5 mIU/L, along with samples from 20 women with TSH levels ≤ 4 mIU/L and 20 pregnancy-week matched women with TSH levels >4 mIU/L. Results: The serum IL-17A levels and ratios of CD4+IL-17A+ cells were significantly lower in women with TSH > 2.5 mIU/L than in those with TSH ≤ 2.5 mIU/L (both P < 0.01). Similar lower differences were noted in women with TSH > 4 mIU/L than in those with TSH ≤ 4 mIU/L (both P < 0.01). Moreover, serum TSH correlated negatively with IL-17A levels (β = -0.195, P = 0.004), but positively with the week of gestation (β = 0.284, P < 0.001). Logistic regression indicated that a lower serum IL-17A level was a risk factor for TSH > 2.5 mIU/L [OR = 0.453 (0.298-0.689), P = 0.000] and TSH > 4.0 mIU/L [OR = 0.588 (0.385-0.899), P = 0.013]. Conclusion: A low serum IL-17A level during the second trimester is associated with an increased risk of TSH > 2.5 mIU/L and subclinical hypothyroidism.

SUBMITTER: He L

PROVIDER: S-EPMC7239996 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BACKGROUND:Subclinical thyroid disease during pregnancy may be associated with adverse outcomes, including a lower-than-normal IQ in offspring. It is unknown whether levothyroxine treatment of women who are identified as having subclinical hypothyroidism or hypothyroxinemia during pregnancy improves cognitive function in their children. METHODS:We screened women with a singleton pregnancy before 20 weeks of gestation for subclinical hypothyroidism, defined as a thyrotropin level of 4.00 mU or more per liter and a normal free thyroxine (T4) level (0.86 to 1.90 ng per deciliter [11 to 24 pmol per liter]), and for hypothyroxinemia, defined as a normal thyrotropin level (0.08 to 3.99 mU per liter) and a low free T4 level (<0.86 ng per deciliter). In separate trials for the two conditions, women were randomly assigned to receive levothyroxine or placebo. Thyroid function was assessed monthly, and the levothyroxine dose was adjusted to attain a normal thyrotropin or free T4 level (depending on the trial), with sham adjustments for placebo. Children underwent annual developmental and behavioral testing for 5 years. The primary outcome was the IQ score at 5 years of age (or at 3 years of age if the 5-year examination was missing) or death at an age of less than 3 years. RESULTS:A total of 677 women with subclinical hypothyroidism underwent randomization at a mean of 16.7 weeks of gestation, and 526 with hypothyroxinemia at a mean of 17.8 weeks of gestation. In the subclinical hypothyroidism trial, the median IQ score of the children was 97 (95% confidence interval [CI], 94 to 99) in the levothyroxine group and 94 (95% CI, 92 to 96) in the placebo group (P=0.71). In the hypothyroxinemia trial, the median IQ score was 94 (95% CI, 91 to 95) in the levothyroxine group and 91 (95% CI, 89 to 93) in the placebo group (P=0.30). In each trial, IQ scores were missing for 4% of the children. There were no significant between-group differences in either trial in any other neurocognitive or pregnancy outcomes or in the incidence of adverse events, which was low in both groups. CONCLUSIONS:Treatment for subclinical hypothyroidism or hypothyroxinemia beginning between 8 and 20 weeks of gestation did not result in significantly better cognitive outcomes in children through 5 years of age than no treatment for those conditions. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institute of Neurological Disorders and Stroke; ClinicalTrials.gov number, NCT00388297 .).

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Low Serum IL-17A in Pregnancy During Second Trimester Is Associated With an Increased Risk of Subclinical Hypothyroidism.

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