{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T05:04:05Z","timestamp":1779685445823,"version":"3.53.1"},"reference-count":26,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T00:00:00Z","timestamp":1779667200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Hypertensive disorders of pregnancy (HDP) threaten maternal and fetal health, and the etiology remains unclear. Previous studies have reported lower plasma aldosterone concentration (PAC) in patients with HDP, but this association remains controversial. The primary objective of this study was to determine the relationship between first-trimester PAC and the risk of HDP.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This prospective, multicenter cohort study recruited eligible pregnant women in their first-trimester from six hospitals in China between May 1, 2023, and December 31, 2024. Inclusion criteria comprised naturally conceived singleton pregnancy with a gestational age of less than 14 weeks. The primary exposure was the baseline PAC measured at first-trimester pregnancy registration. The primary outcome was a clinical diagnosis of HDP. The association was assessed using multivariable logistic regression, adjusting for potential confounders. Potential nonlinearity was explored with restricted cubic splines (RCS), and threshold effects were evaluated using piecewise regression. Sensitivity analyses were conducted to test the robustness of the findings. Statistical analyses were performed using R software (version 4.2.2) and SPSS (version 26.0). A two-sided\n                      <jats:italic>P<\/jats:italic>\n                      -value &amp;lt; 0.050 was considered statistically significant.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A total of 1,486 women were included in the final analysis, of whom 145 (9.8%) developed HDP. Women with HDP had significantly lower first-trimester PAC than those without (median: 18.85 vs. 22.96 ng\/dL,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&amp;lt;\u00a00.001). The RCS analysis revealed a significant nonlinear relationship between PAC and HDP risk (\n                      <jats:italic>P<\/jats:italic>\n                      for nonlinearity = 0.005). Piecewise regression identified a threshold at 39.30 ng\/dL: below it, each 1 ng\/dL increase in PAC was associated with a 3.8% reduction in the odds of HDP (adjusted odds ratio [OR], 0.962, 95% confidence interval [CI]: 0.939\u20130.985,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.001); at or above it, the association was positive but not significant (adjusted OR, 1.027, 95% CI: 0.995\u20131.060,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.098). These findings remained consistent across multiple sensitivity analyses.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>First-trimester PAC exhibited a nonlinear association with HDP risk, with an inflection point at 39.30 ng\/dL. Below this threshold, higher PAC was significantly associated with a lower risk of HDP. At or above this level, the association was positive but not statistically significant.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2026.1836569","type":"journal-article","created":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T04:46:07Z","timestamp":1779684367000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Nonlinear association between first-trimester plasma aldosterone concentration and risk of hypertensive disorders of pregnancy: a multicenter prospective cohort study"],"prefix":"10.3389","volume":"17","author":[{"given":"Nanfang","family":"Li","sequence":"first","affiliation":[{"name":"Hypertension Center of People\u2019s Hospital of Xinjiang Uygur Autonomous Region, Xinjiang Hypertension Institute, NHC Key Laboratory of Hypertension Clinical Research, Key Laboratory of Xinjiang Uygur Autonomous Region \u201cHypertension Research Laboratory\u201d, Xinjiang Clinical Medical Research Center for Hypertension (Cardio-Cerebrovascular) Diseases","place":["Urumqi, Xinjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei","family":"Yang","sequence":"additional","affiliation":[{"name":"Hypertension Center of People\u2019s Hospital of Xinjiang Uygur Autonomous Region, Xinjiang Hypertension Institute, NHC Key Laboratory of Hypertension Clinical Research, Key Laboratory of Xinjiang Uygur Autonomous Region \u201cHypertension Research Laboratory\u201d, Xinjiang Clinical Medical Research Center for Hypertension (Cardio-Cerebrovascular) Diseases","place":["Urumqi, Xinjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinxuan","family":"Ren","sequence":"additional","affiliation":[{"name":"Hypertension Center of People\u2019s Hospital of Xinjiang Uygur Autonomous Region, Xinjiang Hypertension Institute, NHC Key Laboratory of Hypertension Clinical Research, Key Laboratory of Xinjiang Uygur Autonomous Region \u201cHypertension Research Laboratory\u201d, Xinjiang Clinical Medical Research Center for Hypertension (Cardio-Cerebrovascular) Diseases","place":["Urumqi, Xinjiang, China"]},{"name":"Xinjiang Medical University","place":["Urumqi, Xinjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Menghui","family":"Wang","sequence":"additional","affiliation":[{"name":"Hypertension Center of People\u2019s Hospital of Xinjiang Uygur Autonomous Region, Xinjiang Hypertension Institute, NHC Key Laboratory of Hypertension Clinical Research, Key Laboratory of Xinjiang Uygur Autonomous Region \u201cHypertension Research Laboratory\u201d, Xinjiang Clinical Medical Research Center for Hypertension (Cardio-Cerebrovascular) Diseases","place":["Urumqi, Xinjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Zhu","sequence":"additional","affiliation":[{"name":"Hypertension Center of People\u2019s Hospital of Xinjiang Uygur Autonomous Region, Xinjiang Hypertension Institute, NHC Key Laboratory of Hypertension Clinical Research, Key Laboratory of Xinjiang Uygur Autonomous Region \u201cHypertension Research Laboratory\u201d, Xinjiang Clinical Medical Research Center for Hypertension (Cardio-Cerebrovascular) Diseases","place":["Urumqi, Xinjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingxuan","family":"Guo","sequence":"additional","affiliation":[{"name":"Hypertension Center of People\u2019s Hospital of Xinjiang Uygur Autonomous Region, Xinjiang Hypertension Institute, NHC Key Laboratory of Hypertension Clinical Research, Key Laboratory of Xinjiang Uygur Autonomous Region \u201cHypertension Research Laboratory\u201d, Xinjiang Clinical Medical Research Center for Hypertension (Cardio-Cerebrovascular) Diseases","place":["Urumqi, Xinjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Wu","sequence":"additional","affiliation":[{"name":"Hypertension Center of People\u2019s Hospital of Xinjiang Uygur Autonomous Region, Xinjiang Hypertension Institute, NHC Key Laboratory of Hypertension Clinical Research, Key Laboratory of Xinjiang Uygur Autonomous Region \u201cHypertension Research Laboratory\u201d, Xinjiang Clinical Medical Research Center for Hypertension (Cardio-Cerebrovascular) Diseases","place":["Urumqi, Xinjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Lin","sequence":"additional","affiliation":[{"name":"Hypertension Center of People\u2019s Hospital of Xinjiang Uygur Autonomous Region, Xinjiang Hypertension Institute, NHC Key Laboratory of Hypertension Clinical Research, Key Laboratory of Xinjiang Uygur Autonomous Region \u201cHypertension Research Laboratory\u201d, Xinjiang Clinical Medical Research Center for Hypertension (Cardio-Cerebrovascular) Diseases","place":["Urumqi, Xinjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,25]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"388","DOI":"10.1186\/s12884-017-1575-2","article-title":"Perinatal outcomes of hypertensive disorders in pregnancy at a tertiary hospital in Ghana","volume":"17","author":"Adu-Bonsaffoh","year":"2017","journal-title":"BMC Preg Childb"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1161\/jaha.120.016357","article-title":"Patterns of postpartum ambulatory care follow-up care among women with hypertensive disorders of pregnancy","volume":"9","author":"Lewey","year":"2020","journal-title":"J Am Heart Assoc"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.cjca.2022.05.007","article-title":"Development and internal validation of a risk prediction model for acute cardiovascular morbidity in preeclampsia","volume":"38","author":"Malham\u00e9","year":"2022","journal-title":"Can J Cardiol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1007\/s12630-016-0689-8","article-title":"Hypertensive disorders of pregnancy","volume":"63","author":"Sjaus","year":"2016","journal-title":"Can J Anaesth"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1097\/aog.0000000000003370","article-title":"Severe maternal morbidity among stillbirth and live birth deliveries in California","volume":"134","author":"Wall-Wieler","year":"2019","journal-title":"Obstet Gynecol"},{"key":"B6","doi-asserted-by":"publisher","first-page":"e88","DOI":"10.1161\/hypertensionaha.124.23765","article-title":"Epidemiology of maternal hypertensive disorders","volume":"82","author":"Zhao","year":"2025","journal-title":"Hypertension"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1161\/hypertensionaha.118.12137","article-title":"Role of corin in blood pressure regulation in normotensive and hypertensive pregnancy","volume":"73","author":"Badrov","year":"2019","journal-title":"Hypertension"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1186\/s13148-018-0482-3","article-title":"Competing endogenous RNA expression profiling in pre-eclampsia identifies hsa_circ_0036877 as a potential novel blood biomarker for early pre-eclampsia","volume":"10","author":"Hu","year":"2018","journal-title":"Clin Epigenet"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1007\/s00404-024-07393-6","article-title":"Advances in pathogenesis of preeclampsia","volume":"309","author":"Yang","year":"2024","journal-title":"Arch Gynecol Obstet"},{"key":"B10","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1007\/s11906-021-01147-4","article-title":"Combined oral contraceptive pill-induced hypertension and hypertensive disorders of pregnancy: Shared mechanisms and clinical similarities","volume":"23","author":"Gunaratne","year":"2021","journal-title":"Curr Hypertens Rep"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2020.596145","article-title":"Current researches, rationale, plausibility, and evidence gaps on metformin for the management of hypertensive disorders of pregnancy","volume":"11","author":"Zhang","year":"2020","journal-title":"Front Pharmacol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1097\/aog.0000000000003891","article-title":"Gestational hypertension and preeclampsia: ACOG practice bulletin, number 222","volume":"135","year":"2020","journal-title":"Obstet Gynecol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1097\/ee9.0000000000000149","article-title":"Drinking water contaminants in California and hypertensive disorders in pregnancy","volume":"5","author":"Padula","year":"2021","journal-title":"Environ Epidemiol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0239048","article-title":"Prevalence and determinants of hypertensive disorders of pregnancy in Ethiopia: A systematic review and meta-analysis","volume":"15","author":"Tesfa","year":"2020","journal-title":"PloS One"},{"key":"B15","doi-asserted-by":"publisher","first-page":"424","DOI":"10.3390\/toxics11050424","article-title":"Associations between air pollution exposure and blood pressure during pregnancy among PRINCESA cohort participants","volume":"11","author":"Buxton","year":"2023","journal-title":"Toxics"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1001\/jama.280.19.1690","article-title":"What's the relative risk? A method of correcting the odds ratio in cohort studies of common outcomes","volume":"280","author":"Zhang","year":"1998","journal-title":"Jama"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1055\/a-2025-0510","article-title":"Renin, aldosterone, and cortisol in pregnancy-induced hypertension","volume":"131","author":"Lewandowski","year":"2023","journal-title":"Exp Clin Endocrinol Diabetes"},{"key":"B18","doi-asserted-by":"publisher","first-page":"12728","DOI":"10.3390\/ijms241612728","article-title":"Activation of the renin-angiotensin-aldosterone system is attenuated in hypertensive compared with normotensive pregnancy","volume":"24","author":"Shoemaker","year":"2023","journal-title":"Int J Mol Sci"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.14744\/scie.2016.03264","article-title":"First trimester renin and aldosterone levels of pregnant women with prognosis of preeclampsia and\/or related adverse pregnancy outcomes","author":"Purut","year":"2017","journal-title":"South Clinics Istanbul Eurasia"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1161\/hypertensionaha.119.12924","article-title":"Aldosterone, salt, and potassium intakes as predictors of pregnancy outcome, including preeclampsia","volume":"74","author":"Birukov","year":"2019","journal-title":"Hypertension"},{"key":"B21","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1016\/j.placenta.2022.03.129","article-title":"Effects of aldosterone on the human placenta: Insights from placental perfusion studies","volume":"123","author":"Mistry","year":"2022","journal-title":"Placenta"},{"key":"B22","doi-asserted-by":"publisher","first-page":"892","DOI":"10.3390\/jcm14030892","article-title":"Renal function and the role of the renin-angiotensin-aldosterone system (RAAS) in normal pregnancy and pre-eclampsia","volume":"14","author":"Tsikouras","year":"2025","journal-title":"J Clin Med"},{"key":"B23","doi-asserted-by":"publisher","first-page":"B2","DOI":"10.1016\/j.ajog.2020.05.010","article-title":"Society for Maternal-Fetal Medicine Consult Series #52: Diagnosis and management of fetal growth restriction: (Replaces Clinical Guideline Number 3, April 2012)","volume":"223","author":"Martins","year":"2020","journal-title":"Am J Obstet Gynecol"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1210\/en.2010-0525","article-title":"Regulation of placental growth by aldosterone and cortisol","volume":"152","author":"Gennari-Moser","year":"2011","journal-title":"Endocrinology"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1111\/j.1464-5491.2010.03087.x","article-title":"Hypoglycaemia increases aldosterone in a dose-dependent fashion","volume":"27","author":"Adler","year":"2010","journal-title":"Diabetes Med"},{"key":"B26","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1093\/ajh\/hpaa137","article-title":"Aldosterone, inflammation, immune system, and hypertension","volume":"34","author":"Ferreira","year":"2021","journal-title":"Am J Hypertens"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2026.1836569\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T04:46:16Z","timestamp":1779684376000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2026.1836569\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,25]]},"references-count":26,"alternative-id":["10.3389\/fendo.2026.1836569"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2026.1836569","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,25]]},"article-number":"1836569"}}