University of Oulu

Toloza, F. J. K., Derakhshan, A., Männistö, T., Bliddal, S., Popova, P. V., Carty, D. M., Chen, L., Taylor, P., Mosso, L., Oken, E., Suvanto, E., Itoh, S., Kishi, R., Bassols, J., Auvinen, J., López-Bermejo, A., Brown, S. J., Boucai, L., Hisada, A., … Maraka, S. (2022). Association between maternal thyroid function and risk of gestational hypertension and pre-eclampsia: A systematic review and individual-participant data meta-analysis. The Lancet Diabetes & Endocrinology, 10(4), 243–252. https://doi.org/10.1016/S2213-8587(22)00007-9

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
Publish Date: 2023-02-23
Description:

Abstract

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.

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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/
  https://creativecommons.org/licenses/by-nc-nd/4.0/