Browsing by Author "Delles, Christian"

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    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.
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    Association of maternal thyroid function with birthweight: a systematic review and individual-participant data meta-analysis
    (2020) Derakhshan, Arash; Peeters, Robin P.; Taylor, Peter N.; Bliddal, Sofie; Carty, David M.; Meems, Margreet; Vaidya, Bijay; Chen, Liangmiao; Knight, Bridget A.; Ghafoor, Farkhanda; Popova, Polina V.; Mosso, Lorena; Oken, Emily; Suvanto, Eila; Hisada, Aya; Yoshinaga, Jun; Brown, Suzanne J.; Bassols, Judit; Auvinen, Juha; Bramer, Wichor M.; Lopez-Bermejo, Abel; Dayan, Colin M.; French, Robert; Boucai, Laura; Vafeiadi, Marina; Grineva, Elena N.; Pop, Victor J. M.; Vrijkotte, Tanja G.; Chatzi, Leda; Sunyer, Jordi; Jimenez-Zabala, Ana; Riano, Isolina; Rebagliato, Marisa; Lu, Xuemian; Pirzada, Amna; Mannisto, Tuija; Delles, Christian; Feldt-Rasmussen, Ulla; Alexander, Erik K.; Nelson, Scott M.; Chaker, Layal; Pearce, Elizabeth N.; Guxens, Monica; Steegers, Eric A. P.; Walsh, John P.; Korevaar, Tim I. M.
    Background Adequate transplacental passage of maternal thyroid hormone is important for normal fetal growth and development. Maternal overt hypothyroidism and hyperthyroidism are associated with low birthweight, but important knowledge gaps remain regarding the effect of subclinical thyroid function test abnormalities on birthweight-both in general and during the late second and third trimester of pregnancy. The aim of this study was to examine associations of maternal thyroid function with birthweight.
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    Association of Thyroid Function Test Abnormalities and Thyroid Autoimmunity With Preterm Birth A Systematic Review and Meta-analysis
    (2019) Korevaar, Tim I. M.; Derakhshan, Arash; Taylor, Peter N.; Meima, Marcel; Chen, Liangmiao M.; Bliddal, Sofie; Carty, David M.; Meems, Margreet; Vaidya, Bijay; Mosso Gómez, Lorena; Shields, Beverley; Ghafoor, Farkhanda; Popova, Polina V.; Oken, Emily; Suvanto, Eila; Hisada, Aya; Yoshinaga, Jun; Brown, Suzanne J.; Bassols, Judith; Auvinen, Juha; Bramer, Wichor M.; López Bermejo, Abel; Dayan, Colin; Boucai, Laura; Vafeiadi, Marina; Grineva, Elena N.; Tkachuck, Alexandra S.; Pop, Victor J. M.; Vrijkotte, Tanja G.; Guxens, Mònica; Chatzi, Leda; Sunyer, Jordi; Jiménez Zabala, Ana; Riaño, Isolina; Murcia, Mario; Lu, Xuemian M.; Mukhtar, Shafqat; Delles, Christian; Feldt Rasmussen, Ulla; Nelson, Scott M.; Alexander, Erik K.; Chaker, Layal; Mannisto, Tuija; Walsh, John P.; Pearce, Elizabeth N.; Steegers, Eric A. P.; Peeters, Robin P.
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    Genome-Wide Association Study of Blood Pressure Extremes Identifies Variant near UMOD Associated with Hypertension
    (PUBLIC LIBRARY SCIENCE, 2010) Padmanabhan, Sandosh; Melander, Olle; Johnson, Toby; Di Blasio, Anna Maria; Lee, Wai K.; Gentilini, Davide; Hastie, Claire E.; Menni, Cristina; Monti, Maria Cristina; Delles, Christian; Laing, Stewart; Corso, Barbara; Navis, Gerjan; Kwakernaak, Arjan J.; van der Harst, Pim; Bochud, Murielle; Maillard, Marc; Burnier, Michel; Hedner, Thomas; Kjeldsen, Sverre; Wahlstrand, Bjorn; Sjogren, Marketa; Fava, Cristiano; Montagnana, Martina; Danese, Elisa; Torffvit, Ole; Hedblad, Bo; Snieder, Harold; Connell, John M. C.; Brown, Morris; Samani, Nilesh J.; Farrall, Martin; Cesana, Giancarlo; Mancia, Giuseppe; Signorini, Stefano; Grassi, Guido; Eyheramendy, Susana; Wichmann, H. Erich; Laan, Maris; Strachan, David P.; Sever, Peter; Shields, Denis Colm; Stanton, Alice; Vollenweider, Peter; Teumer, Alexander; Voelzke, Henry; Rettig, Rainer; Newton Cheh, Christopher; Arora, Pankaj; Zhang, Feng; Soranzo, Nicole; Spector, Timothy D.; Lucas, Gavin; Kathiresan, Sekar; Siscovick, David S.; Luan, Jian'an; Loos, Ruth J. F.; Wareham, Nicholas J.; Penninx, Brenda W.; Nolte, Ilja M.; McBride, Martin; Miller, William H.; Nicklin, Stuart A.; Baker, Andrew H.; Graham, Delyth; McDonald, Robert A.; Pell, Jill P.; Sattar, Naveed; Welsh, Paul; Munroe, Patricia; Caulfield, Mark J.; Zanchetti, Alberto; Dominiczak, Anna F.; Global BPgen Consortium
    Hypertension is a heritable and major contributor to the global burden of disease. The sum of rare and common genetic variants robustly identified so far explain only 1%-2% of the population variation in BP and hypertension. This suggests the existence of more undiscovered common variants. We conducted a genome-wide association study in 1,621 hypertensive cases and 1,699 controls and follow-up validation analyses in 19,845 cases and 16,541 controls using an extreme case-control design. We identified a locus on chromosome 16 in the 59 region of Uromodulin (UMOD; rs13333226, combined P value of 3.6x10(-11)). The minor G allele is associated with a lower risk of hypertension (OR [95% CI]: 0.87 [0.84-0.91]), reduced urinary uromodulin excretion, better renal function; and each copy of the G allele is associated with a 7.7% reduction in risk of CVD events after adjusting for age, sex, BMI, and smoking status (H.R. = 0.923, 95% CI 0.860-0.991; p = 0.027). In a subset of 13,446 individuals with estimated glomerular filtration rate (eGFR) measurements, we show that rs13333226 is independently associated with hypertension (unadjusted for eGFR: 0.89 [0.83-0.96], p = 0.004; after eGFR adjustment: 0.89 [0.83-0.96], p = 0.003). In clinical functional studies, we also consistently show the minor G allele is associated with lower urinary uromodulin excretion. The exclusive expression of uromodulin in the thick portion of the ascending limb of Henle suggests a putative role of this variant in hypertension through an effect on sodium homeostasis. The newly discovered UMOD locus for hypertension has the potential to give new insights into the role of uromodulin in BP regulation and to identify novel drugable targets for reducing cardiovascular risk.