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    Preconception management of hyperthyroidism and thyroid status in subsequent pregnancy: a population-based cohort study
    (Endocrine Society, 2023-05-01) Minassian, C.; Allen, L. A.; Okosieme, O.; Vaidya, B.; Taylor, P.
    CONTEXT: Optimal thyroid status in pregnancy is essential in reducing the risk of adverse outcomes. The management of hyperthyroidism in women of reproductive age poses unique challenges and it is unclear how preconception treatment strategies impact on thyroid status in subsequent pregnancy. METHODS: We utilised the Clinical Practice Research Datalink (CPRD) database to evaluate all females aged 15-45 years, with a clinical diagnosis of hyperthyroidism and a subsequent pregnancy (January 2000 to December 2017). We compared thyroid status in pregnancy according to preconception treatment, namely, (1) antithyroid drugs up to or beyond pregnancy onset, (2) definitive treatment with thyroidectomy or radioiodine before pregnancy, and (3) no treatment at pregnancy onset. RESULTS: Our study cohort comprised 4712 pregnancies. TSH was measured in only 53.1% of pregnancies of which 28.1% showed suboptimal thyroid status (TSH >4.0 mU/L or TSH <0.1 mU/L plus FT4 >reference range). Pregnancies with prior definitive treatment were more likely to have suboptimal thyroid status compared to pregnancies starting during antithyroid drug treatment (OR = 4.72, 95%CI 3.50-6.36). A steady decline in the use of definitive treatment before pregnancy was observed from 2000-2017. A third (32.6%) of first trimester carbimazole-exposed pregnancies were switched to propylthiouracil while 6.0% of propylthiouracil-exposed pregnancies switched to carbimazole. CONCLUSION: The management of women with hyperthyroidism who become pregnant is suboptimal, particularly in those with preconception definitive treatment, and needs urgent improvement. Better thyroid monitoring and prenatal counselling are needed to optimise thyroid status, reduce teratogenic drug exposure, and ultimately reduce the risk of adverse pregnancy outcomes.
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    TSH and FT4 reference intervals in pregnancy: a systematic review and individual participant data meta-analysis
    (Endocrine Society, 2022-07-21) Osinga, J. A. J.; Derakhshan, A.; Palomaki, G. E.; Ashoor, G.; Männistö, T.; Maraka, S.; Chen, L.; Bliddal, S.; Lu, X.; Taylor, P. N.; Vrijkotte, T. G. M.; Tao, F. B.; Brown, S. J.; Ghafoor, F.; Poppe, K.; Veltri, F.; Chatzi, L.; Vaidya, B.; Broeren, M. A. C.; Shields, B. M.; Itoh, S.; Mosso, L.; Popova, P. V.; Anopova, A. D.; Kishi, R.; Aminorroaya, A.; Kianpour, M.; López-Bermejo, A.; Oken, E.; Pirzada, A.; Vafeiadi, M.; Bramer, W. M.; Suvanto, E.; Yoshinaga, J.; Huang, K.; Bassols, J.; Boucai, L.; Feldt-Rasmussen, U.; Grineva, E. N.; Pearce, E. N.; Alexander, E. K.; Pop, V. J. M.; Nelson, S. M.; Walsh, J. P.; Peeters, R. P.; Chaker, L.; Nicolaides, K. H.; D'Alton, M. E.; Korevaar, T. I. M.
    CONTEXT: Interpretation of thyroid function tests during pregnancy is limited by the generalizability of reference intervals between cohorts due to inconsistent methodology. OBJECTIVE: 1) To provide an overview of published reference intervals for TSH and FT4 in pregnancy, 2) to assess the consequences of common methodological between-study differences by combining raw data from different cohorts. METHODS: 1) Ovid MEDLINE, EMBASE and Web of Science were searched until the 12th of December 2021. Studies were assessed in duplicate. 2) The individual participant data (IPD) meta-analysis was performed in participating cohorts in the Consortium on Thyroid and Pregnancy. RESULTS: 1) Large between-study methodological differences were identified, 11 of 102 included studies were in accordance with current guidelines. 2) 22 cohorts involving 63,198 participants, were included in the meta-analysis. Not excluding TPOAb-positive participants led to a rise of the upper limits of TSH in all cohorts, especially in the first (mean: +17.4%[range +1.6 to +30.3%]) and second trimester (mean: +9.8% [range +0.6 to +32.3%]). The use of the 95th percentile led to considerable changes in upper limits, varying from -10.8% to -21.8% for TSH and -1.2% to -13.2% for FT4. All other additional exclusion criteria changed reference interval cut-offs by a maximum of 3.5%. Applying these findings to the 102 studies included in the systematic review, 48 studies could be used in a clinical setting. CONCLUSIONS: We provide an overview of clinically relevant reference intervals for TSH and FT4 in pregnancy. The results of the meta-analysis indicate that future studies can adopt a simplified study setup without additional exclusion criteria.