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      The Impact of Subclinical Hypothyroidism on Adverse Perinatal Outcomes and the Role of Thyroid Screening in Pregnancy

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          Abstract

          Subclinical hypothyroidism (SCH) is a mild form of hypothyroidism that is common among women of childbearing age. The impact of SCH on adverse perinatal outcomes is unclear and universal screening for thyroid function before or during pregnancy is also much debated. In the present retrospective cohort study on 7,587 women from Shanghai, we assessed whether SCH was associated with adverse perinatal outcomes. The relationship between the risks of adverse outcomes and the time of screening and LT4 treatment status for SCH were also evaluated. SCH was associated with hypertensive disorders of pregnancy (HDP) [odds ratio (OR): 4.04; 95% confidence interval (CI): 1.85–8.84; P = 0.000]. After classification into four different groups based on the time of screening for thyroid function, the increased likelihood of HDP persisted in those diagnosed with SCH in the first and second trimesters (OR: 9.69; 95% CI: 1.73–54.48; P = 0.01 and OR: 3.66; 95% CI: 1.07–12.57, P = 0.03, respectively). The diagnosis of SCH in the preconception period and the third trimester was not significantly associated with HDP and other adverse perinatal outcomes. Five out of 120 (5/120) treated women (4.17%) vs. 4/45 untreated women (8.89%) developed HDP, 4/5 were treated after conception. The results indicate that during pregnancy, SCH conferred an increased risk of HDP, particularly in women diagnosed with the disorder in the first and second trimesters.

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          Most cited references30

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          Laboratory medicine practice guidelines. Laboratory support for the diagnosis and monitoring of thyroid disease.

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            Antenatal thyroid screening and childhood cognitive function.

            Children born to women with low thyroid hormone levels have been reported to have decreased cognitive function. We conducted a randomized trial in which pregnant women at a gestation of 15 weeks 6 days or less provided blood samples for measurement of thyrotropin and free thyroxine (T(4)). Women were assigned to a screening group (in which measurements were obtained immediately) or a control group (in which serum was stored and measurements were obtained shortly after delivery). Thyrotropin levels above the 97.5th percentile, free T(4) levels below the 2.5th percentile, or both were considered a positive screening result. Women with positive findings in the screening group were assigned to 150 μg of levothyroxine per day. The primary outcome was IQ at 3 years of age in children of women with positive results, as measured by psychologists who were unaware of the group assignments. Of 21,846 women who provided blood samples (at a median gestational age of 12 weeks 3 days), 390 women in the screening group and 404 in the control group tested positive. The median gestational age at the start of levothyroxine treatment was 13 weeks 3 days; treatment was adjusted as needed to achieve a target thyrotropin level of 0.1 to 1.0 mIU per liter. Among the children of women with positive results, the mean IQ scores were 99.2 and 100.0 in the screening and control groups, respectively (difference, 0.8; 95% confidence interval [CI], -1.1 to 2.6; P=0.40 by intention-to-treat analysis); the proportions of children with an IQ of less than 85 were 12.1% in the screening group and 14.1% in the control group (difference, 2.1 percentage points; 95% CI, -2.6 to 6.7; P=0.39). An on-treatment analysis showed similar results. Antenatal screening (at a median gestational age of 12 weeks 3 days) and maternal treatment for hypothyroidism did not result in improved cognitive function in children at 3 years of age. (Funded by the Wellcome Trust UK and Compagnia di San Paulo, Turin; Current Controlled Trials number, ISRCTN46178175.).
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              Treatment of Subclinical Hypothyroidism or Hypothyroxinemia in Pregnancy.

              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.
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                Author and article information

                Contributors
                Journal
                Front Endocrinol (Lausanne)
                Front Endocrinol (Lausanne)
                Front. Endocrinol.
                Frontiers in Endocrinology
                Frontiers Media S.A.
                1664-2392
                06 August 2019
                2019
                : 10
                : 522
                Affiliations
                [1] 1MOE, Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine , Shanghai, China
                [2] 2Department of Nuclear Medicine, Shanghai Tenth People's Hospital, Tongji University , Shanghai, China
                [3] 3School of Public Health, Shanghai Jiao Tong University School of Medicine , Shanghai, China
                [4] 4The Women and Children's Health Care Department, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine , Shanghai, China
                Author notes

                Edited by: Alex Stewart Stagnaro-Green, University of Illinois at Chicago, United States

                Reviewed by: Spyridoula Maraka, University of Arkansas for Medical Sciences, United States; Mohd Shazli Shazli Draman, Cardiff University, United Kingdom

                *Correspondence: Chong-Huai Yan yanchonghuai@ 123456xinhuamed.com.cn

                This article was submitted to Thyroid Endocrinology, a section of the journal Frontiers in Endocrinology

                †These authors have contributed equally to this work

                Article
                10.3389/fendo.2019.00522
                6691141
                31447778
                1ae5707c-c2c5-486e-b21b-f8703f5f0a02
                Copyright © 2019 Wu, Liu, Wang, Yang, Yan and Hua.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 06 May 2019
                : 16 July 2019
                Page count
                Figures: 1, Tables: 4, Equations: 0, References: 33, Pages: 8, Words: 5505
                Funding
                Funded by: National Natural Science Foundation of China 10.13039/501100001809
                Funded by: Shanghai Municipal Health Bureau 10.13039/501100007279
                Categories
                Endocrinology
                Original Research

                Endocrinology & Diabetes
                subclinical hypothyroidism,pregnancy,hypertensive disorders of pregnancy,thyroid function,thyroid function screening

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