{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,24]],"date-time":"2025-09-24T08:07:36Z","timestamp":1758701256196,"version":"3.44.0"},"reference-count":32,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,8,14]],"date-time":"2025-08-14T00:00:00Z","timestamp":1755129600000},"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. Pediatr."],"abstract":"<jats:sec><jats:title>Background\/Objectives<\/jats:title><jats:p>Pregnancy complications are associated with adverse maternal\u2013neonatal outcomes, but the underlying immune mechanisms remain unclear. Here we examined umbilical cord IL-17A levels and their link to gestational diabetes mellitus (GDM) and perinatal infections (PIs).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This two-phase study analyzed 87 pregnant women (38 in the exploratory phase and 49 in the validation phase) from Shenzhen's Premature Infants Gut Microbiota Assembly and Neurodevelopment (PIGMAN) cohort, divided into perinatal complication (PC) (45 cases) and non-perinatal complication (NPC) (42 cases) groups. Cord blood IL-17A levels were measured by ELISA and analyzed as a continuous variable by Nonparametric rank-sum test and a categorical variable using Fisher's exact test.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Nonparametric analysis revealed consistently lower IL-17A levels in the PC group across both phases. The discovery phase median in the PC group was 0.67\u2005pg\/ml lower than the 5.68\u2005pg\/ml median in the NPC group (<jats:italic>p<\/jats:italic>\u2009=\u20090.001); in the validation phase, the PC and NPC group levels were 0.93 and 2.05\u2005pg\/ml (<jats:italic>p<\/jats:italic>\u2009=\u20090.012), respectively. Low IL-17A (&amp;lt;1\u2005pg\/ml) prevalence was significantly higher in PC cases (discovery: 61.9% vs. 11.8%, <jats:italic>p<\/jats:italic>\u2009=\u20090.002; validation: 50% vs. 36%, <jats:italic>p<\/jats:italic>\u2009=\u20090.031). Rank-sum test and Fisher's exact test demonstrated concordant results, confirming a robust association between reduced IL-17A levels and perinatal complications.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Umbilical cord blood from PC pregnancies exhibited significantly lower IL-17A levels compared to that from NPC pregnancies, suggesting compromised neonatal cellular immunity. These findings implicate IL-17A deficiency in the immune dysregulation associated with GDM and PI. Conversely, the higher IL-17A levels observed in NPC pregnancies may reflect its protective role in maternal\u2013fetal immunity during early development.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fped.2025.1658039","type":"journal-article","created":{"date-parts":[[2025,8,14]],"date-time":"2025-08-14T05:35:47Z","timestamp":1755149747000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Reduced IL-17A levels in neonates born to mothers with diabetes mellitus or infection during pregnancy"],"prefix":"10.3389","volume":"13","author":[{"given":"Tingting","family":"Li","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sufen","family":"Hu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fangfang","family":"Guo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Youming","family":"He","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haiping","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mengying","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Mao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kexin","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan","family":"Lin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rui","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Defei","family":"Ma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shiting","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cheng","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bing","family":"Hu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mingbang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yingmei","family":"Xie","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,8,14]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"675","DOI":"10.1111\/apa.16651","article-title":"Perinatal risk factors for developmental coordination disorder in children born extremely preterm","volume":"112","author":"Bolk","year":"2023","journal-title":"Acta Paediatr"},{"key":"B2","doi-asserted-by":"publisher","first-page":"439","DOI":"10.1016\/j.pedneo.2020.03.016","article-title":"Perinatal risk factors of symptomatic preterm patent ductus arteriosus and secondary ligation","volume":"61","author":"Lee","year":"2020","journal-title":"Pediatr Neonatol"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1526","DOI":"10.1111\/apa.16356","article-title":"Perinatal risk factors for mortality in very preterm infants-a nationwide, population-based discriminant analysis","volume":"111","author":"Norman","year":"2022","journal-title":"Acta Paediatr"},{"key":"B4","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1007\/s12519-019-00322-7","article-title":"Perinatal risk factors for pulmonary hemorrhage in extremely low-birth-weight infants","volume":"16","author":"Wang","year":"2020","journal-title":"World J Pediatr"},{"key":"B5","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1186\/s12884-018-1810-5","article-title":"Pregnancy outcomes in women with gestational diabetes mellitus diagnosed according to the WHO-2013 and WHO-1999 diagnostic criteria: a multicentre retrospective cohort study","volume":"18","author":"Goedegebure","year":"2018","journal-title":"BMC Pregnancy Childbirth"},{"key":"B6","doi-asserted-by":"publisher","first-page":"e00285","DOI":"10.1002\/edm2.285","article-title":"Gestational diabetes mellitus (GDM) and adverse pregnancy outcome in south Asia: a systematic review","volume":"4","author":"Mistry","year":"2021","journal-title":"Endocrinol Diabetes Metab"},{"key":"B7","doi-asserted-by":"publisher","first-page":"3","DOI":"10.4093\/dmj.2021.0335","article-title":"Gestational diabetes mellitus: diagnostic approaches and maternal-offspring complications","volume":"46","author":"Moon","year":"2022","journal-title":"Diabetes Metab J"},{"key":"B8","doi-asserted-by":"publisher","first-page":"763","DOI":"10.1210\/endrev\/bnac003","article-title":"A clinical update on gestational diabetes mellitus","volume":"43","author":"Sweeting","year":"2022","journal-title":"Endocr Rev"},{"key":"B9","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1080\/21622965.2013.874951","article-title":"Gestational diabetes: long-term central nervous system developmental and cognitive sequelae","volume":"4","author":"Perna","year":"2015","journal-title":"Appl Neuropsychol Child"},{"key":"B10","doi-asserted-by":"publisher","first-page":"507","DOI":"10.1002\/cbin.11955","article-title":"Dominant immune cells in pregnancy and pregnancy complications: t helper cells (TH1\/TH2, TH17\/treg cells), NK cells, MDSCs, and the immune checkpoints","volume":"47","author":"Esparvarinha","year":"2023","journal-title":"Cell Biol Int"},{"key":"B11","doi-asserted-by":"publisher","first-page":"718168","DOI":"10.3389\/fimmu.2021.718168","article-title":"MAIT cells balance the requirements for immune tolerance and anti-microbial defense during pregnancy","volume":"12","author":"Raffetseder","year":"2021","journal-title":"Front Immunol"},{"key":"B12","doi-asserted-by":"publisher","first-page":"346","DOI":"10.1016\/j.humimm.2021.01.019","article-title":"The role of decidual regulatory T cells in the induction and maintenance of fetal antigen-specific tolerance: imbalance between regulatory and cytotoxic T cells in pregnancy complications","volume":"82","author":"Tsuda","year":"2021","journal-title":"Hum Immunol"},{"key":"B13","doi-asserted-by":"publisher","first-page":"3706","DOI":"10.4049\/jimmunol.1502613","article-title":"Lipopolysaccharide-induced chorioamnionitis promotes IL-1-dependent inflammatory FOXP3+ CD4+ T cells in the fetal rhesus macaque","volume":"196","author":"Rueda","year":"2016","journal-title":"J Immunol"},{"key":"B14","doi-asserted-by":"publisher","first-page":"140","DOI":"10.1186\/s12933-019-0935-9","article-title":"Predictive and diagnostic biomarkers for gestational diabetes and its associated metabolic and cardiovascular diseases","volume":"18","author":"Lorenzo-Almor\u00f3s","year":"2019","journal-title":"Cardiovasc Diabetol"},{"key":"B15","doi-asserted-by":"publisher","first-page":"1660","DOI":"10.1007\/s00125-021-05447-x","article-title":"Oestrogen receptor \u03b1 in T cells controls the T cell immune profile and glucose metabolism in mouse models of gestational diabetes mellitus","volume":"64","author":"Tanaka","year":"2021","journal-title":"Diabetologia"},{"key":"B16","doi-asserted-by":"publisher","first-page":"2025","DOI":"10.3389\/fimmu.2020.02025","article-title":"T Helper (Th) cell profiles in pregnancy and recurrent pregnancy losses: Th1\/Th2\/Th9\/Th17\/Th22\/Tfh cells","volume":"11","author":"Wang","year":"2020","journal-title":"Front Immunol"},{"key":"B17","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1111\/j.1600-0897.2009.00693.x","article-title":"Interleukin-17 increased progesterone secretion by JEG-3 human choriocarcinoma cells","volume":"61","author":"Pongcharoen","year":"2009","journal-title":"Am J Reprod Immunol"},{"key":"B18","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1111\/j.1600-0897.2010.00893.x","article-title":"IL-17 increased in the third trimester in healthy women with term labor","volume":"65","author":"Mart\u00ednez-Garc\u00eda","year":"2011","journal-title":"Am J Reprod Immunol"},{"key":"B19","first-page":"345","article-title":"Association of cord blood levels of IL-17A, but not TGF-\u03b2 with pre-term neonate","volume":"13","author":"Mobini","year":"2015","journal-title":"Iran J Reprod Med"},{"key":"B20","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1034\/j.1600-0897.2003.01150.x","article-title":"Demonstration of the presence of IL-16, IL-17 and IL-18 at the murine fetomaternal interface during murine pregnancy","volume":"49","author":"Ostojic","year":"2003","journal-title":"Am J Reprod Immunol"},{"key":"B21","doi-asserted-by":"publisher","first-page":"623","DOI":"10.1038\/icb.2016.48","article-title":"The majority of murine \u03b3\u03b4 T cells at the maternal-fetal interface in pregnancy produce IL-17","volume":"94","author":"Pinget","year":"2016","journal-title":"Immunol Cell Biol"},{"key":"B22","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1186\/1471-2393-13-65","article-title":"Primary prevention of gestational diabetes for women who are overweight and obese: a randomised controlled trial","volume":"13","author":"Nagle","year":"2013","journal-title":"BMC Pregnancy Childbirth"},{"key":"B23","doi-asserted-by":"publisher","first-page":"6868470","DOI":"10.1155\/2020\/6868470","article-title":"Bushen HuoXue decoction promotes decidual stromal cell proliferation via the PI3K\/AKT pathway in unexplained recurrent spontaneous abortion","volume":"2020","author":"Feng","year":"2020","journal-title":"Evid Based Complement Alternat Med"},{"key":"B24","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1016\/j.biopha.2018.02.103","article-title":"The potential pathogenic role of IL-17\/Th17 cells in both type 1 and type 2 diabetes mellitus","volume":"101","author":"Abdel-Moneim","year":"2018","journal-title":"Biomed Pharmacother"},{"key":"B25","doi-asserted-by":"publisher","first-page":"252ra120","DOI":"10.1126\/scitranslmed.3008791","article-title":"Breast-fed and bottle-fed infant rhesus macaques develop distinct gut microbiotas and immune systems","volume":"6","author":"Ardeshir","year":"2014","journal-title":"Sci Transl Med"},{"key":"B26","doi-asserted-by":"publisher","first-page":"569","DOI":"10.1126\/science.1241165","article-title":"The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis","volume":"341","author":"Smith","year":"2013","journal-title":"Science"},{"key":"B27","doi-asserted-by":"publisher","first-page":"1358144","DOI":"10.3389\/fendo.2024.1358144","article-title":"Is there a causal association between gestational diabetes mellitus and immune mediators? A bidirectional Mendelian randomization analysis","volume":"15","author":"Ji","year":"2024","journal-title":"Front Endocrinol"},{"key":"B28","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1016\/j.bpobgyn.2021.03.007","article-title":"Uptake of vaccination in pregnancy","volume":"76","author":"Sebghati","year":"2021","journal-title":"Best Pract Res Clin Obstet Gynaecol"},{"key":"B29","doi-asserted-by":"publisher","first-page":"564","DOI":"10.1038\/cmi.2014.54","article-title":"TH17 cells in human recurrent pregnancy loss and pre-eclampsia","volume":"11","author":"Fu","year":"2014","journal-title":"Cell Mol Immunol"},{"key":"B30","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1111\/j.1600-0897.2009.00771.x","article-title":"Circulating and decidual Th17 cell levels in healthy pregnancy","volume":"63","author":"Nakashima","year":"2010","journal-title":"Am J Reprod Immunol"},{"key":"B31","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1111\/j.1600-0897.2006.00366.x","article-title":"The effect of interleukin-17 on the proliferation and invasion of JEG-3 human choriocarcinoma cells","volume":"55","author":"Pongcharoen","year":"2006","journal-title":"Am J Reprod Immunol"},{"key":"B32","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1111\/imm.12595","article-title":"The T helper type 17\/regulatory T cell paradigm in pregnancy","volume":"148","author":"Figueiredo","year":"2016","journal-title":"Immunology"}],"container-title":["Frontiers in Pediatrics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fped.2025.1658039\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,14]],"date-time":"2025-08-14T05:35:49Z","timestamp":1755149749000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fped.2025.1658039\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,14]]},"references-count":32,"alternative-id":["10.3389\/fped.2025.1658039"],"URL":"https:\/\/doi.org\/10.3389\/fped.2025.1658039","relation":{},"ISSN":["2296-2360"],"issn-type":[{"value":"2296-2360","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,14]]},"article-number":"1658039"}}