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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 |
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| Author: | Toloza, Freddy J K1,2,3; Derakhshan, Arash4,5; Männistö, Tuija6,7; |
| Organizations: |
1Division of Endocrinology and Metabolism, University of Arkansas for Medical Sciences, Little Rock, AR, USA 2Knowledge and Evaluation Research Unit, Division of Endocrinology, Diabetes, Metabolism and Nutrition, Department of Medicine, Mayo Clinic, Rochester, MN, USA 3Department of Medicine, MetroWest Medical Center, Tufts Medical School, Framingham, MA, USA
4Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, Netherlands
5Academic Center for Thyroid Diseases, Erasmus University Medical Center, Rotterdam, Netherlands 6Medical Research Center Oulu, Oulu University Hospital, University of Oulu, Oulu, Finland 7Northern Finland Laboratory Center Nordlab, University of Oulu, Oulu, Finland 8Department of Medical Endocrinology and Metabolism, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark 9Department of Endocrinology, Almazov National Medical Research Centre, Saint Petersburg, Russia 10Institute of Endocrinology, Almazov National Medical Research Centre, Saint Petersburg, Russia 11World-Class Research Center for Personalized Medicine, Almazov National Medical Research Centre, Saint Petersburg, Russia 12Department of Internal Diseases and Endocrinology, St Petersburg Pavlov State Medical University, Saint Petersburg, Russia 13Department of Diabetes, Endocrinology and Clinical Pharmacology, Glasgow Royal Infirmary, Glasgow, UK 14Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK 15Department of Endocrinology and Rui'an Center of the Chinese-American Research Institute for Diabetic Complications, Third Affiliated Hospital of Wenzhou Medical University, Wenzhou, China 16Thyroid Research Group, Institute of Molecular and Experimental Medicine, School of Medicine, Cardiff University, Cardiff, UK 17Department of Endocrinology and Centro Traslacional en Endocrinologia, Pontificia Universidad Catolica de Chile, Santiago, Chile 18Division of Chronic Disease Research Across the Lifecourse, Department of Population Medicine, Harvard Medical School, Boston, MA, USA 19Department of Obstetrics and Gynecology, University of Oulu, Oulu, Finland 20Center for Environmental and Health Sciences, Hokkaido University, Sapporo, Japan 21Maternal-Fetal Metabolic Research Group, Girona Biomedical Research Institute, Dr Josep Trueta Hospital, Girona, Spain 22Center for Life Course Health Research, University of Oulu, Oulu, Finland 23Pediatric Endocrinology Research Group, Girona Biomedical Research Institute, Dr Josep Trueta Hospital, Girona, Spain 24Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Nedlands, WA, Australia 25Division of Endocrinology, Department of Medicine, Memorial Sloan-Kettering Cancer Center, Weill Cornell University, New York, NY, USA 26Center for Preventive Medical Sciences, Chiba University, Chiba, Japan 27Faculty of Life Sciences, Toyo University, Gunma, Japan 28Department of Gynecology and Endocrinology, DO Ott Research Institute of Obstetrics and Gynecology, Saint Petersburg, Russia 29Department of Public Health, Amsterdam UMC, University of Amsterdam, Amsterdam Public Health Research Institute, Amsterdam, Netherlands 30ISGlobal, Barcelona, Spain 31Pompeu Fabra University, Barcelona, Spain 32Hospital del Mar Medical Research Institute, Barcelona, Spain 33Spanish Consortium for Research on Epidemiology and Public Health, Instituto de Salud Carlos III, Madrid, Spain 34BIODONOSTIA Health Research Institute, San Sebastian, Spain 35Public Health Division of Gipuzkoa, Basque Government, San Sebastian, Spain 36AGC Pediatrics, Hospital Universitario Central de Asturias, Oviedo, Spain 37IUOPA-Departamento de Medicina-ISPA, Universidad de Oviedo, Oviedo, Spain 38Epidemiology and Environmental Health Joint Research Unit, FISABIO–Universitat Jaume I–Universitat de València, Valencia, Spain 39Faculty of Nursing and Chiropody, Universitat de València, Valencia, Spain 40Mayo Clinic Libraries, Mayo Clinic, Rochester, MN, USA 41Division of Endocrinology, Department of Medicine, University of Florida, Gainesville, FL, USA 42Division of Endocrinology, Department of Internal Medicine, University Hospital Dr Jose E Gonzalez, Autonomous University of Nuevo León, Monterrey, Mexico 43Plataforma INVEST Medicina UANL-KER Unit, Universidad Autónoma de Nuevo León, Monterrey, México 44Division of Endocrinology, Hypertension and Diabetes, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA 45Section of Endocrinology, Diabetes, and Nutrition, Boston University School of Medicine, Boston, MA, USA 46Department of Child and Adolescent Psychiatry/Psychology, Erasmus University Medical Center, Rotterdam, Netherlands 47Department of Population and Public Health Sciences, University of Southern California, Keck School of Medicine, Los Angeles, CA, USA 48Department of Medical and Clinical Psychology, Tilburg University, Tilburg, Netherlands 49Medical School, University of Western Australia, Crawley, WA, Australia 50School of Medicine, University of Glasgow, Glasgow, UK 51Central Arkansas Veterans Healthcare System, Little Rock, AR, USA |
| Format: | article |
| Version: | accepted version |
| Access: | open |
| Online Access: | PDF Full Text (PDF, 1.3 MB) |
| Persistent link: | http://urn.fi/urn:nbn:fi-fe2023022328485 |
| Language: | English |
| Published: |
Elsevier,
2022
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| Publish Date: | 2023-02-23 |
| Description: |
AbstractBackground: 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. see all
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| Series: |
The Lancet. Diabetes & endocrinology |
| ISSN: | 2213-8587 |
| ISSN-E: | 2213-8595 |
| ISSN-L: | 2213-8587 |
| Volume: | 10 |
| Issue: | 4 |
| Pages: | 243 - 252 |
| DOI: | 10.1016/S2213-8587(22)00007-9 |
| OADOI: | https://oadoi.org/10.1016/S2213-8587(22)00007-9 |
| Type of Publication: |
A1 Journal article – refereed |
| Field of Science: |
3121 General medicine, internal medicine and other clinical medicine 3123 Gynaecology and paediatrics |
| Subjects: | |
| Funding: |
Arkansas Biosciences Institute and Netherlands Organization for Scientific Research. |
| Copyright information: |
© 2022. This manuscript version is made available under the CC-BY-NC-ND 4.0 license https://creativecommons.org/licenses/by-nc-nd/4.0/ |
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https://creativecommons.org/licenses/by-nc-nd/4.0/ |