Browsing by Author "Taylor, Peter"

Now showing 1 - 3 of 3
  • No Thumbnail Available
    Item
    Association between maternal thyroid function and risk of gestational hypertension and pre-eclampsia: a systematic review and individual-participant data meta-analysis
    (2022) Toloza, Freddy J. K.; Derakhshan, Arash; Mannisto, Tuija; Bliddal, Sofie; Popova, Polina, V; Carty, David M.; Chen, Liangmiao; Taylor, Peter; Mosso, Lorena; Oken, Emily; Suvanto, Eila; Itoh, Sachiko; Kishi, Reiko; Bassols, Judit; Auvinen, Juha; Lopez-Bermejo, Abel; Brown, Suzanne J.; Boucai, Laura; Hisada, Aya; Yoshinaga, Jun; Shilova, Ekaterina; Grineva, Elena N.; Vrijkotte, Tanja G. M.; Sunyer, Jordi; Jimenez-Zabala, Ana; Riano-Galan, Isolina; Lopez-Espinosa, Maria-Jose; Prokop, Larry J.; Ospina, Naykky Singh; Brito, Juan P.; Rodriguez-Gutierrez, Rene; Alexander, Erik K.; Chaker, Layal; Pearce, Elizabeth N.; Peeters, Robin P.; Feldt-Rasmussen, Ulla; Guxens, Monica; Chatzi, Leda; Delles, Christian; van Lennep, Jeanine E. Roeters; Pop, Victor J. M.; Lu, Xuemian; Walsh, John P.; Nelson, Scott M.; Korevaar, Tim I. M.; Maraka, Spyridoula
    Background Adequate maternal thyroid function is important for an uncomplicated pregnancy. Although multiple observational studies have evaluated the association between thyroid dysfunction and hypertensive disorders of pregnancy, the methods and definitions of abnormalities in thyroid function tests were heterogeneous, and the results were conflicting. We aimed to examine the association between abnormalities in thyroid function tests and risk of gestational hypertension and pre-eclampsia. Methods In this systematic review and meta-analysis of individual-participant data, we searched MEDLINE (Ovid), Embase, Scopus, and the Cochrane Database of Systematic Reviews from date of inception to Dec 27, 2019, for prospective cohort studies with data on maternal concentrations of thyroid-stimulating hormone (TSH), free thyroxine (FT4), thyroid peroxidase (TPO) antibodies, individually or in combination, as well as on gestational hypertension, pre-eclampsia, or both. We issued open invitations to study authors to participate in the Consortium on Thyroid and Pregnancy and to share the individual-participant data. We excluded participants who had pre-existing thyroid disease or multifetal pregnancy, or were taking medications that affect thyroid function. The primary outcomes were documented gestational hypertension and pre-eclampsia. Individual-participant data were analysed using logistic mixed-effects regression models adjusting for maternal age, BMI, smoking, parity, ethnicity, and gestational age at blood sampling. The study protocol was registered with PROSPERO, CRD42019128585. Findings We identified 1539 published studies, of which 33 cohorts met the inclusion criteria and 19 cohorts were included after the authors agreed to participate. Our study population comprised 46 528 pregnant women, of whom 39 826 (85.6%) women had sufficient data (TSH and FT4 concentrations and TPO antibody status) to be classified according to their thyroid function status. Of these women, 1275 (3.2%) had subclinical hypothyroidism, 933 (2.3%) had isolated hypothyroxinaemia, 619 (1.6%) had subclinical hyperthyroidism, and 337 (0.8%) had overt hyperthyroidism. Compared with euthyroidism, subclinical hypothyroidism was associated with a higher risk of pre-eclampsia (2.1% vs 3.6%; OR 1.53 [95% CI 1.09-2.15]). Subclinical hyperthyroidism, isolated hypothyroxinaemia, or TPO antibody positivity were not associated with gestational hypertension or pre-eclampsia. In continuous analyses, both a higher and a lower TSH concentration were associated with a higher risk of pre-eclampsia (p=0.0001). FT4 concentrations were not associated with the outcomes measured. Interpretation Compared with euthyroidism, subclinical hypothyroidism during pregnancy was associated with a higher risk of pre-eclampsia. There was a U-shaped association of TSH with pre-eclampsia. These results quantify the risks of gestational hypertension or pre-eclampsia in women with thyroid function test abnormalities, adding to the total body of evidence on the risk of adverse maternal and fetal outcomes of thyroid dysfunction during pregnancy. These findings have potential implications for defining the optimal treatment target in women treated with levothyroxine during pregnancy, which needs to be assessed in future interventional studies. Copyright (C) 2022 Elsevier Ltd. All righst reserved.
  • No Thumbnail Available
    Item
    Association of Thyroid Peroxidase Antibodies and Thyroglobulin Antibodies with Thyroid Function in Pregnancy: An Individual Participant Data Meta-Analysis
    (2022) Bliddal, Sofie; Derakhshan, Arash; Xiao, Yi; Chen, Liang-Miao; Mannisto, Tuija; Ashoor, Ghalia; Tao, Fangbiao; Brown, Suzanne J.; Vafeiadi, Marina; Itoh, Sachiko; Grineva, Elena Nikolaevna; Taylor, Peter; Ghafoor, Farkhanda; Vaidya, Bijay; Hattersley, Andrew; Mosso, Lorena; Oken, Emily; Kishi, Reiko; Alexander, Erik K.; Maraka, Spyridoula; Huang, Kun; Chaker, Layal; Bassols, Judit; Pirzada, Amna; Lopez-Bermejo, Abel; Boucai, Laura; Peeters, Robin P.; Pearce, Elizabeth N.; Nelson, Scott McGill; Chatzi, Leda; Vrijkotte, Tanja G.; Popova, Polina V.; Walsh, John P.; Nicolaides, Kypros H.; Suvanto, Eila; Lu, Xuemian; Pop, Victor J. M.; Forman, Julie Lyng; Korevaar, Tim I. M.; Feldt-Rasmussen, Ulla
    Objectives: Thyroid autoimmunity is common in pregnant women and associated with thyroid dysfunction and adverse obstetric outcomes. Most studies focus on thyroid peroxidase antibodies (TPOAbs) assessed by a negative-positive dichotomy and rarely take into account thyroglobulin antibodies (TgAbs). This study aimed at determining the association of TPOAbs and TgAbs, respectively, and interdependently, with maternal thyroid function.Methods: This was a meta-analysis of individual participant cross-sectional data from 20 cohorts in the Consortium on Thyroid and Pregnancy. Women with multiple pregnancy, pregnancy by assisted reproductive technology, history of thyroid disease, or use of thyroid interfering medication were excluded. Associations of (log2) TPOAbs and TgAbs (with/without mutual adjustment) with cohort-specific z-scores of (log2) thyrotropin (TSH), free triiodothyronine (fT3), total triiodothyronine (TT3), free thyroxine (fT4), total thyroxine (TT4), or triiodothyronine:thyroxine (T3:T4) ratio were evaluated in a linear mixed model.Results: In total, 51,138 women participated (51,094 had TPOAb-data and 27,874 had TgAb-data). Isolated TPOAb positivity was present in 4.1% [95% confidence interval, CI: 3.0 to 5.2], isolated TgAb positivity in 4.8% [CI: 2.9 to 6.6], and positivity for both antibodies in 4.7% [CI: 3.1 to 6.3]. Compared with antibody-negative women, TSH was higher in women with isolated TPOAb positivity (z-score increment 0.40, CI: 0.16 to 0.64) and TgAb positivity (0.21, CI: 0.10 to 0.32), but highest in those positive for both antibodies (0.54, CI: 0.36 to 0.71). There was a dose-response effect of higher TPOAb and TgAb concentrations with higher TSH (TSH z-score increment for TPOAbs 0.12, CI: 0.09 to 0.15, TgAbs 0.08, CI: 0.02 to 0.15). When adjusting analyses for the other antibody, only the association of TPOAbs remained statistically significant. A higher TPOAb concentration was associated with lower fT4 (p < 0.001) and higher T3:T4 ratio (0.09, CI: 0.03 to 0.14), however, the association with fT4 was not significant when adjusting for TgAbs (p = 0.16).Conclusions: This individual participant data meta-analysis demonstrated an increase in TSH with isolated TPOAb positivity and TgAb positivity, respectively, which was amplified for individuals positive for both antibodies. There was a dose-dependent association of TPOAbs, but not TgAbs, with TSH when adjusting for the other antibody. This supports current practice of using TPOAbs in initial laboratory testing of pregnant women suspected of autoimmune thyroid disease. However, studies on the differences between TPOAb- and TgAb-positive women are needed to fully understand the spectrum of phenotypes.
  • Thumbnail Image
    Item
    Synthesis, characterization and biological activity of platinum(II) complexes with a tetrapyrazole ligand
    (PERGAMON-ELSEVIER SCIENCE LTD, 2015) Higuera Padilla, Angel R.; Capote, Jorlis; Ortega, Dianela; Castro, William; Rodriguez Cordero, Mildred; Coll, David; Hernandez Medina, Fernando; Fernandez Mestre, Mercedes; Urdanibia, Izaskun; Taylor, Peter; Rodriguez, Barbara; Karam, Arquimedes
    In the search of an effective chemotherapy for the treatment of cancer, in this work we describe the synthesis, characterization and biological activity of two new platinum complexes. The general formula is [Pt-2(L)(X)(4)], where L was 1,2,4,5-tetrakis((1H-pyrazol-1-yl)methyl)benzene and X were iodine (1) and chlorine (2). The most probable structure was established through a combination of spectroscopic analysis and density functional theory (DFT) calculations. Studies of interaction of complexes with DNA were carried out, and the results by spectroscopic titrations, thermal denaturation and viscosity, showed noncovalent interactions of complexes with DNA. The comet assay showed damage to cellular DNA Inhibition assays of thioredoxin reductase (TrxR) were carried out, and the compounds showed notable inhibitory activity on the enzyme in a concentration dependent manner, with IC50 values of 3.9 and 3.5 nM for 1 and 2 respectively. Complex 2 exhibited greater inhibitory effects than complex 1 against all the tumor cell lines, with growth inhibitory effects superior to cisplatin in some cases. (C) 2015 Elsevier Ltd. All rights reserved.