{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T20:17:54Z","timestamp":1792181874167,"version":"4.4.0"},"reference-count":30,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T00:00:00Z","timestamp":1778630400000},"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>Objective<\/jats:title>\n                    <jats:p>To investigate the independent and joint effects of gestational diabetes mellitus (GDM) and hypertensive disorders of pregnancy (HDP) on adverse pregnancy outcomes, evaluate their potential interaction, and explore the nonlinear dose\u2013response relationships between blood glucose and blood pressure levels and composite adverse outcomes using a restricted cubic spline (RCS) model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This retrospective cohort study included 240 women who delivered at Dongyang Maternal and Child Health Hospital between January 2020 and December 2024. Participants were categorized into four groups according to the presence of GDM and\/or HDP: control, GDM only, HDP only, and comorbid GDM + HDP. The primary outcome was a composite of adverse pregnancy outcomes, including preterm birth, Apgar score &amp;lt; 7, neonatal intensive care unit (NICU) admission, and fetal growth abnormalities. Multivariable logistic regression models were applied to estimate adjusted odds ratios (aORs) and 95% confidence intervals (CIs). Additive interaction indices\u2014relative excess risk due to interaction (RERI) and attributable proportion (AP)\u2014were calculated to assess synergistic effects. Nonlinear dose\u2013response associations between mean fasting glucose, systolic blood pressure (SBP).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Compared with the control group, HDP was independently associated with a higher risk of composite adverse outcomes (aOR = 3.30, 95% CI: 1.41\u20137.70, P\u00a0=\u00a00.006), while comorbid GDM + HDP showed a substantially elevated risk (aOR = 9.25, 95% CI: 2.63\u201332.45, P &amp;lt; 0.001). Additive interaction analysis demonstrated a significant positive interaction between GDM and HDP (RERI\u00a0=\u00a05.62; AP\u00a0=\u00a00.61), suggesting that over half of the excess risk was attributable to their joint effect. Specifically, the risks of preterm birth and small-for-gestational-age infants increased markedly in the HDP and comorbid groups, whereas GDM alone was primarily associated with large-for-gestational-age outcomes. RCS analysis revealed a nonlinear positive relationship between mean SBP and composite adverse outcomes, with the risk increasing sharply beyond approximately 135 mmHg and accelerating above 160 mmHg.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Both GDM and HDP independently increase the risk of adverse pregnancy outcomes, and their coexistence exerts a synergistic effect that amplifies maternal and neonatal risk. The nonlinear dose\u2013response pattern between SBP and adverse outcomes highlights that even mild elevations in blood pressure can have detrimental effects.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2026.1805525","type":"journal-article","created":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T04:50:45Z","timestamp":1778647845000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Impact of gestational diabetes mellitus and hypertensive disorders of pregnancy on adverse pregnancy outcomes: a retrospective cohort study"],"prefix":"10.3389","volume":"17","author":[{"given":"Junjia","family":"Shao","sequence":"first","affiliation":[{"name":"Department of Obstetrical, Dongyang Maternal and Child Health Hospital","place":["Jinhua, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xia","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Obstetrical, Dongyang Maternal and Child Health Hospital","place":["Jinhua, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lifeng","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Obstetrical, Dongyang Maternal and Child Health Hospital","place":["Jinhua, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Obstetrical, Dongyang Maternal and Child Health Hospital","place":["Jinhua, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,13]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabres.2021.109050","article-title":"IDF Diabetes Atlas: Global and regional estimate of gestational diabetes mellitus prevalence for 2019\u20132021 by International Association of Diabetes in Pregnancy Study Group's criteria","volume":"183","author":"Wang","year":"2021","journal-title":"Diabetes Res Clin Pract"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1","DOI":"10.21203\/rs.3.rs-146936\/v1","article-title":"Epidemiological trends of maternal hypertensive disorders of pregnancy at the global, regional, and national levels: a population\u2010based study","volume":"21","author":"Wang","year":"2021","journal-title":"BMC Pregnancy Childbirth"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.3390\/jcm12113852","article-title":"Association between HbA1c levels and fetal macrosomia and large for gestational age babies in women with gestational diabetes mellitus: a systematic review and meta-analysis of 17,711 women","volume":"12","author":"Mou","year":"2023","journal-title":"J Clin Med"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.eclinm.2024.102861","article-title":"Prediction of adverse maternal and perinatal outcomes associated with pre-eclampsia and hypertensive disorders of pregnancy: a systematic review and meta-analysis","volume":"76","author":"Bucher","year":"2024","journal-title":"eClinicalMedicine"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabres.2020.108642","article-title":"Increasing prevalence of gestational diabetes mellitus when implementing the IADPSG criteria: a systematic review and meta-analysis","volume":"172","author":"Saeedi","year":"2020","journal-title":"Diabetes Res Clin Pract"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.cpcardiol.2023.101982","article-title":"Hypertensive disorders in pregnancy: global burden from 1990 to 2019, current research hotspots and emerging trends","volume":"48","author":"Fu","year":"2023","journal-title":"Curr Probl Cardiol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/s2666-7568(22)00292-6","article-title":"Cardiovascular mortality in women in their forties after hypertensive disorders of pregnancy in the Netherlands: a national cohort study","volume":"4","author":"Welters","year":"2023","journal-title":"Lancet Healthy Longevity"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1530\/ey.19.2.17","article-title":"Persistence of risk for type 2 diabetes after gestational diabetes mellitus","volume":"45","author":"Diaz-Santana","year":"2022","journal-title":"Diabetes Care"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.jri.2023.104161","article-title":"Placenta and maternal endothelium during preeclampsia: Disruption of the glycocalyx explains increased inositol phosphoglycans and angiogenic factors in maternal blood","volume":"160","author":"Scioscia","year":"2023","journal-title":"J Reprod Immunol"},{"key":"B10","doi-asserted-by":"publisher","first-page":"569593","DOI":"10.3389\/fendo.2020.00655","article-title":"Mechanisms of endothelial dysfunction in pre-eclampsia and gestational diabetes mellitus: Windows into future cardiometabolic health","volume":"11","author":"McElwain","year":"2020","journal-title":"Front Endocrinol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2023.04.003","article-title":"Missing links in preeclampsia cell model systems of endothelial dysfunction","volume":"29","author":"Viana-Mattioli","year":"2023","journal-title":"Trends Mol Med"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2024.1468820","article-title":"Association of the comorbidity of gestational diabetes mellitus and hypertension disorders of pregnancy with birth outcomes","volume":"15","author":"Lin","year":"2024","journal-title":"Front Endocrinol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.xagr.2025.100571","article-title":"Hypertensive disorders of pregnancy and gestational diabetes mellitus affect fetal growth and perinatal outcomes in women undergoing In Vitro fertilization","volume":"5","author":"Su","year":"2025","journal-title":"AJOG Global Rep"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1007\/s10654-011-9554-9","article-title":"Estimating measures of interaction on an additive scale for preventive exposures","volume":"26","author":"Knol","year":"2011","journal-title":"Eur J Epidemiol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyaf088","article-title":"Estimating and presenting non-linear associations with restricted cubic splines","volume":"54","author":"Discacciati","year":"2025","journal-title":"Int J Epidemiol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.3389\/fepid.2022.975380","article-title":"Modeling non-linear relationships in epidemiological data: The application and interpretation of spline models","volume":"2","author":"Schuster","year":"2022","journal-title":"Front Epidemiol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2023.1130116","article-title":"Setting a stage: Inflammation during preeclampsia and postpartum","volume":"14","author":"Herrock","year":"2023","journal-title":"Front Physiol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpc.2025.101054","article-title":"Preeclampsia: Insights into pathophysiological mechanisms and preventive strategies","volume":"23","author":"Martini","year":"2025","journal-title":"Am J Prev Cardiol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1136\/bmj-2021-067946","article-title":"Gestational diabetes mellitus and adverse pregnancy outcomes: systematic review and meta-analysis","volume":"377","author":"Ye","year":"2022","journal-title":"Br Med J"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2021.659733","article-title":"O-GlcNAcylation in hyperglycemic pregnancies: Impact on placental function","volume":"12","author":"Ning","year":"2021","journal-title":"Front Endocrinol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2022.43618","article-title":"Association of concomitant gestational hypertensive disorders and gestational diabetes with cardiovascular disease","volume":"5","author":"Tcheugui","year":"2022","journal-title":"JAMA Netw Open"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.3390\/antiox12101894","article-title":"Inflammation and oxidative stress induced by obesity, gestational diabetes, and preeclampsia in pregnancy: Role of high-density lipoproteins as vectors for bioactive compounds","volume":"12","author":"Jim\u00e9nez-Osorio","year":"2023","journal-title":"Antioxidants"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1038\/s41440-023-01570-x","article-title":"The association between blood pressure control in women during pregnancy and adverse perinatal outcomes: the TMM BirThree Cohort Study","volume":"47","author":"Ishikuro","year":"2024","journal-title":"Hypertens Res"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1080\/14767058.2023.2296366","article-title":"Association of pre-\/early pregnancy high blood pressure and pregnancy outcomes: a systemic review and meta-analysis","volume":"37","author":"Jin","year":"2023","journal-title":"J Matern Fetal Neonatal Med"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.2337\/dc11-1790","article-title":"Hyperglycemia and adverse pregnancy outcomes: The HAPO Study Cooperative Research Group","volume":"63","year":"2008","journal-title":"Obstet Gynecol Surv"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1097\/01.aoa.0000515731.59684.57","article-title":"Hyperglycaemia and risk of adverse perinatal outcomes: systematic review and meta-analysis","volume":"37","author":"Farrar","year":"2017","journal-title":"Obstetric Anesth Digest"},{"key":"B27","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s40001-023-01024-7","article-title":"Aspirin 75 mg to prevent preeclampsia in high-risk pregnancies: a retrospective real-world study in China","volume":"28","author":"Xiao","year":"2023","journal-title":"Eur J Med Res"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2023.1111371","article-title":"Application of low dose aspirin in pre-eclampsia","volume":"10","author":"Ren","year":"2023","journal-title":"Front Med"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1161\/jaha.123.033252","article-title":"Early mortality, cardiovascular, and renal diseases in women's lives following hypertensive disorders of pregnancy: The prospective nationwide study CONCEPTION","volume":"13","author":"Lailler","year":"2024","journal-title":"J Am Heart Assoc"},{"key":"B30","doi-asserted-by":"publisher","first-page":"897","DOI":"10.1161\/hypertensionaha.123.22081","article-title":"Incident cardiovascular disease in women with type 1 or type 2 diabetes following a hypertensive disorder of pregnancy","volume":"81","author":"Mattsson","year":"2024","journal-title":"Hypertension"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2026.1805525\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T04:50:52Z","timestamp":1778647852000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2026.1805525\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,13]]},"references-count":30,"alternative-id":["10.3389\/fendo.2026.1805525"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2026.1805525","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,13]]},"article-number":"1805525"}}