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      Maternal TSH levels at first trimester and subsequent spontaneous miscarriage: a nested case–control study

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          Abstract

          Thyroid dysfunction is a frequently found endocrine disorder among reproductively aged women. Subclinical hypothyroidism is the most common condition of thyroid disorders during pregnancy and is defined as manifesting a thyroid-stimulating hormone concentration exceeding the trimester-specific reference value, with a normal free thyroxine concentration. Here, we evaluated the prospective association between spontaneous miscarriage and first-trimester thyroid function. We conducted a case–control study (421 cases and 1684 controls) that was nested. Thyroid-stimulating hormone (TSH), free thyroxine (FT 4), thyroid-peroxidase antibody (TPOAb) and thyroglobulin antibody (TgAb) status were measured. We found that higher TSH was related to spontaneous miscarriage (OR 1.21; 95% CI, 1.13–1.30, P < 0.001). Compared with women with TSH levels of 0.4–<2.5 mIU/L, the risk of miscarriage was increased in women with TSH levels of 2.5–<4.87 mIU/L (OR 1.47; 95% CI, 1.16–1.87) and TSH greater than 4.87 mIU/L (OR 1.97; 95% CI, 1.22–3.18). After controlling for the confounding factor, TPOAb positivity status and FT 4, the results were similar. The present study showed that higher TSH was associated with miscarriage in early pregnancy. In fact, TSH levels between 2.5 and 4.87 mIU/L increased the risk for miscarriage, with TSH greater than 4.87 mIU/L increasing the risk even further.

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          Subclinical hypothyroidism and pregnancy outcomes.

          Clinical thyroid dysfunction has been associated with pregnancy complications such as hypertension, preterm birth, low birth weight, placental abruption, and fetal death. The relationship between subclinical hypothyroidism and pregnancy outcomes has not been well studied. We undertook this prospective thyroid screening study to evaluate pregnancy outcomes in women with elevated thyrotropin (thyroid-stimulating hormone, TSH) and normal free thyroxine levels. All women who presented to Parkland Hospital for prenatal care between November 1, 2000, and April 14, 2003, had thyroid screening using a chemiluminescent TSH assay. Women with TSH values at or above the 97.5th percentile for gestational age at screening and with free thyroxine more than 0.680 ng/dL were retrospectively identified with subclinical hypothyroidism. Pregnancy outcomes were compared with those in pregnant women with normal TSH values between the 5th and 95th percentiles. A total of 25,756 women underwent thyroid screening and were delivered of a singleton infant. There were 17,298 (67%) women enrolled for prenatal care at 20 weeks of gestation or less, and 404 (2.3%) of these were considered to have subclinical hypothyroidism. Pregnancies in women with subclinical hypothyroidism were 3 times more likely to be complicated by placental abruption (relative risk 3.0, 95% confidence interval 1.1-8.2). Preterm birth, defined as delivery at or before 34 weeks of gestation, was almost 2-fold higher in women with subclinical hypothyroidism (relative risk, 1.8, 95% confidence interval 1.1-2.9). We speculate that the previously reported reduction in intelligence quotient of offspring of women with subclinical hypothyroidism may be related to the effects of prematurity. II-2.
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            Significance of (sub)clinical thyroid dysfunction and thyroid autoimmunity before conception and in early pregnancy: a systematic review.

            Thyroid dysfunction and thyroid autoimmunity are prevalent among women of reproductive age and are associated with adverse pregnancy outcomes. Preconception or early pregnancy screening for thyroid dysfunction has been proposed but is not widely accepted. We conducted a systematic review of the literature on the clinical significance of thyroid dysfunction and thyroid autoimmunity before conception and in early pregnancy. Relevant studies were identified by searching Medline, EMBASE and the Cochrane Controlled Trials Register. From a total of 14 208 primary selected titles, 43 articles were included for the systematic review and 38 were appropriate for meta-analyses. No articles about hyperthyroidism were selected. Subclinical hypothyroidism in early pregnancy, compared with normal thyroid function, was associated with the occurrence of pre-eclampsia [odds ratio (OR) 1.7, 95% confidence interval (CI) 1.1-2.6] and an increased risk of perinatal mortality (OR 2.7, 95% CI 1.6-4.7). In the meta-analyses, the presence of thyroid antibodies was associated with an increased risk of unexplained subfertility (OR 1.5, 95% CI 1.1-2.0), miscarriage (OR 3.73, 95% CI 1.8-7.6), recurrent miscarriage (OR 2.3, 95% CI 1.5-3.5), preterm birth (OR 1.9, 95% CI 1.1-3.5) and maternal post-partum thyroiditis (OR 11.5, 95% CI 5.6-24) when compared with the absence of thyroid antibodies. Pregnant women with subclinical hypothyroidism or thyroid antibodies have an increased risk of complications, especially pre-eclampsia, perinatal mortality and (recurrent) miscarriage. Future research, within the setting of clinical trials, should focus on the potential health gain of identification, and effect of treatment, of thyroid disease on pregnancy outcome.
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              Abnormalities of maternal thyroid function during pregnancy affect neuropsychological development of their children at 25-30 months.

              To examine the relationship between specific thyroid abnormalities (subclinical hypothyroidism, hypothyroxinaemia or elevated thyroid peroxidase antibody titres) in women during pregnancy and the subsequent neuropsychological development of their offspring. Serum was collected from 1268 women at 16-20 weeks of gestation and thyroid stimulating hormone (TSH), total thyroxine (tT(4)), free thyroxine (fT(4)), and Thyroid peroxidase antibodies (TPOAb) levels were measured. Thyroid function reference ranges specific for pregnancy were used to screen for thyroid abnormalities. Patients with isolated subclinical hypothyroidism (18 cases), hypothyroxinaemia (19 cases), and those who were euthyroid patients with elevated titres of TPOAb (34 cases) were identified. One hundred and forty-two euthyroid and TPOAb-negative women matched for gestational age from the same cohort were selected as controls. Intellectual and motor development score evaluations were performed on the children from the pregnancies at 25-30 months of age. Children of women with subclinical hypothyroidism, hypothyroxinemia and elevated TPOAb titres had mean intelligence scores 8.88, 9.30 and 10.56 points lower than those of the control group (P = 0.008, P = 0.004 and P = 0.001, respectively); mean motor scores were 9.98, 7.57 and 9.03 points lower than those of the controls [P < 0.001, P = 0.007 and P < 0.001, respectively (t-test)]. Unconditional multivariate logistic regression analysis showed that increased maternal serum TSH, decreased maternal serum tT(4), and elevated maternal TPOAb titres were separately associated with lower intelligence scores (ORs 15.63, 12.98, and 6.69, respectively) and poorer motor scores (ORs 9.23, 5.52, and 8.25, respectively). Intellectual and motor development of children at 25-30 months of age is separately associated with abnormalities of maternal thyroid at 16-20 weeks gestation. Maternal subclinical hypothyroidism, hypothyroxinaemia or euthyroidism with elevated TPOAb titres were all statistically significant predictors of lower motor and intellectual development at 25-30 months.

                Author and article information

                Journal
                Endocr Connect
                Endocr Connect
                EC
                Endocrine Connections
                Bioscientifica Ltd (Bristol )
                2049-3614
                September 2019
                05 August 2019
                : 8
                : 9
                : 1288-1293
                Affiliations
                [1 ]Department of Endocrinology and Metabolism , Institute of Endocrinology, Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Affiliated Hospital of China Medical University, China Medical University, Shenyang, Liaoning, China
                [2 ]Department of Endocrinology and Metabolism , The Second Hospital of Dalian Medical University, Dalian, Liaoning, China
                Author notes
                Correspondence should be addressed to W Teng or Z Shan: twp@ 123456vip.163.com or shanzhongyan@ 123456medmail.com.cn
                Article
                EC-19-0316
                10.1530/EC-19-0316
                6765319
                31525729
                ce4ac981-db40-4ebc-88a1-52f771298920
                © 2019 The authors

                This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

                History
                : 26 June 2019
                : 05 August 2019
                Categories
                Research

                thyroid,reproduction
                thyroid, reproduction

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