What is the clinical evidence from this study?

Study design: Case-Control. Population: Congenital Heart Disease (CHD) in fetuses (n=123). Intervention: Amniotic fluid 8-iso-PGF2α measurement vs. Gestational age-matched control pregnancies. Primary outcome: Amniotic fluid 8-iso-PGF2α concentrations (p=<0.001).

What does this research mean for the field?

Fetuses with congenital heart disease have significantly higher amniotic fluid 8-iso-PGF2α concentrations than controls, indicating increased intrauterine oxidative stress. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

This study evaluates the evidence of oxidative stress in fetuses with major congenital heart disease by measuring amniotic fluid biomarker levels.

May 8, 2026Open Access

Elevated Amniotic Fluid 8-Iso-Prostaglandin F2α Reveals Intrauterine Oxidative Stress in Fetuses with Congenital Heart Disease: A Prospective Case–Control Study

Q: What are the key findings of this study?

Fetuses with congenital heart disease had significantly higher amniotic fluid 8-iso-PGF2α concentrations than controls (2849 vs 2088 ng/mg Cr, p<0.001), indicating increased oxidative stress.

Q: What does this research mean for the field?

Fetuses with congenital heart disease have significantly higher amniotic fluid 8-iso-PGF2α concentrations than controls, indicating increased intrauterine oxidative stress. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

Q: What question did this study set out to answer?

This study evaluates the evidence of oxidative stress in fetuses with major congenital heart disease by measuring amniotic fluid biomarker levels.

Key Result

Fetuses with congenital heart disease had significantly higher amniotic fluid 8-iso-PGF2α concentrations than controls (2849 vs 2088 ng/mg Cr, p<0.001), indicating increased oxidative stress.

Key Points

This study evaluates the evidence of oxidative stress in fetuses with major congenital heart disease by measuring amniotic fluid biomarker levels.
Prospective case–control design including 123 fetuses (83 CHD, 40 controls) at a tertiary referral center.
Comparison of amniotic fluid 8-iso-PGF2α concentrations between CHD cases and controls, adjusted for gestational age, maternal factors.
Amniotic fluid samples collected via amniocentesis and analyzed using competitive ELISA.
Fetuses with CHD exhibited significantly higher amniotic fluid 8-iso-PGF2α concentrations (2849 ± 1377 ng/mg Cr) compared to controls (2088 ± 1087 ng/mg Cr, p < 0.001).
Results remain significant after adjustment for gestational age, smoking status, diabetes, and maternal BMI.
No consistent differences were found across various anatomical CHD subgroups.

Study Design

Type

Case-Control (n=123)

Multicenter

Structured PICO

Are amniotic fluid 8-iso-PGF2α concentrations elevated in fetuses with isolated major congenital heart disease compared to controls?

Population

123 fetuses (83 with isolated major congenital heart disease, 40 gestational age-matched controls) at a tertiary CHD referral center.

Comparator

Gestational age-matched pregnancies undergoing amniocentesis for indications unlikely to affect oxidative stress

Outcome

Amniotic fluid 8-iso-PGF2α concentrations (normalized to creatinine)surrogate

Fetuses with congenital heart disease exhibit increased intrauterine oxidative stress, as indicated by elevated amniotic fluid 8-iso-PGF2α levels.

Main Result

Absolute Event Rate: 2849% vs 2088%

p-value: p=<0.001

Abstract

Advances in prenatal diagnosis have improved the perinatal management of congenital heart disease (CHD). 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 F2α (8-iso-PGF2α) serving as a biomarker of oxidative injury. This prospective case–control study aimed to evaluate OS in fetuses with isolated major CHD by comparing amniotic fluid (AF) 8-iso-PGF2α 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-PGF2α 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-PGF2α concentrations than controls (2849 ± 1377 vs. 2088 ± 1087 ng/mg Cr, p = < 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-PGF2α concentrations.