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However postnatal comorbidities still persist due to multifactorial causes, which limits prenatal prediction of individual outcomes. Oxidative stress (OS), particularly lipid peroxidation, has been suggested to play a role in the development and progression of CHD, with 8-iso-prostaglandin F2\u03b1 (8-iso-PGF2\u03b1) serving as a biomarker of oxidative injury. This prospective case\u2013control study aimed to evaluate OS in fetuses with isolated major CHD by comparing amniotic fluid (AF) 8-iso-PGF2\u03b1 concentrations with controls. A total of 123 fetuses (83 CHD, 40 controls) were included at a tertiary CHD referral center. CHD cases were subclassified according to anatomical type and expected fetal brain perfusion under placental circulation. Controls were gestational age-matched pregnancies undergoing amniocentesis for indications unlikely to affect OS. All pregnant women underwent standardized fetal biometry, Doppler assessment, and detailed echocardiography. AF samples were obtained by amniocentesis and analyzed for free 8-iso-PGF2\u03b1 using a competitive ELISA, with values normalized to creatinine. Clinical, obstetric, and Doppler characteristics were comparable between groups. CHD fetuses showed significantly higher AF 8-iso-PGF2\u03b1 concentrations than controls (2849 \u00b1 1377 vs. 2088 \u00b1 1087 ng\/mg Cr, p = &lt; 0.001), and remained significant after adjustment for GA, smoking status, diabetes and maternal age and body mass index (BMI). No consistent differences were observed across anatomical or hemodynamic CHD subgroups. These findings provide the first intrauterine evidence of increased lipid peroxidation in fetuses with CHD as reflected by elevated amniotic fluid 8-iso-PGF2\u03b1 concentrations.<\/jats:p>","DOI":"10.3390\/antiox15050586","type":"journal-article","created":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T07:36:23Z","timestamp":1778052983000},"page":"586","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Elevated Amniotic Fluid 8-Iso-Prostaglandin F2\u03b1 Reveals Intrauterine Oxidative Stress in Fetuses with Congenital Heart Disease: A Prospective Case\u2013Control Study"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7071-3829","authenticated-orcid":false,"given":"Miguel","family":"Arr\u00e1ez","sequence":"first","affiliation":[{"name":"BCNatal Fetal Medicine Research Center (Hospital Cl\u00ednic and Hospital Sant Joan de D\u00e9u), 08950 Barcelona, Spain"},{"name":"Spanish Network in Maternal, Neonatal, Child and Developmental Health Research, RICORS-SAMID, RD24\/0013\/0004, Instituto de Salud Carlos III, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9202-4664","authenticated-orcid":false,"given":"Marta","family":"Camprub\u00ed-Camprub\u00ed","sequence":"additional","affiliation":[{"name":"Neonatology Department, Sant Joan de D\u00e9u Hospital, 08950 Barcelona, Spain"},{"name":"Cardiovascular Research Group, Sant Joan de Deu Research Institute, 08950 Barcelona, Spain"},{"name":"Institut de Recerca Sant Joan de D\u00e9u (IRSJD), 08950 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9875-3593","authenticated-orcid":false,"given":"Mar\u00eda C.","family":"Escobar-Diaz","sequence":"additional","affiliation":[{"name":"Institut de Recerca Sant Joan de D\u00e9u (IRSJD), 08950 Barcelona, Spain"},{"name":"Cardiology Department, Sant Joan de D\u00e9u Hospital, 08950 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Guirado","sequence":"additional","affiliation":[{"name":"BCNatal Fetal Medicine Research Center (Hospital Cl\u00ednic and Hospital Sant Joan de D\u00e9u), 08950 Barcelona, Spain"},{"name":"Spanish Network in Maternal, Neonatal, Child and Developmental Health Research, RICORS-SAMID, RD24\/0013\/0004, Instituto de Salud Carlos III, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6938-9104","authenticated-orcid":false,"given":"Laura","family":"Nogu\u00e9","sequence":"additional","affiliation":[{"name":"BCNatal Fetal Medicine Research Center (Hospital Cl\u00ednic and Hospital Sant Joan de D\u00e9u), 08950 Barcelona, Spain"},{"name":"Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3935-1935","authenticated-orcid":false,"given":"Mar","family":"Bennasar","sequence":"additional","affiliation":[{"name":"BCNatal Fetal Medicine Research Center (Hospital Cl\u00ednic and Hospital Sant Joan de D\u00e9u), 08950 Barcelona, Spain"},{"name":"Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4159-7811","authenticated-orcid":false,"given":"Narc\u00eds","family":"Masoller","sequence":"additional","affiliation":[{"name":"BCNatal Fetal Medicine Research Center (Hospital Cl\u00ednic and Hospital Sant Joan de D\u00e9u), 08950 Barcelona, Spain"},{"name":"Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7422-5240","authenticated-orcid":false,"given":"F\u00e0tima","family":"Crispi","sequence":"additional","affiliation":[{"name":"BCNatal Fetal Medicine Research Center (Hospital Cl\u00ednic and Hospital Sant Joan de D\u00e9u), 08950 Barcelona, Spain"},{"name":"Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain"},{"name":"Centre for Biomedical Research on Rare Diseases (CIBER-ER), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Dolores","family":"G\u00f3mez-Roig","sequence":"additional","affiliation":[{"name":"BCNatal Fetal Medicine Research Center (Hospital Cl\u00ednic and Hospital Sant Joan de D\u00e9u), 08950 Barcelona, Spain"},{"name":"Spanish Network in Maternal, Neonatal, Child and Developmental Health Research, RICORS-SAMID, RD24\/0013\/0004, Instituto de Salud Carlos III, 28040 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