Amniotic Fluid and Umbilical Cord Serum Erythropoietin as Biomarkers of Fetal Hypoxia in Term and Prolonged Pregnancies
Background: Prolonged pregnancy is associated with increased risks of fetal hypoxia and adverse perinatal outcomes. Conventional fetal surveillance methods have limited ability to detect subclinical intrauterine hypoxic stress. Erythropoietin (EPO), a hypoxia-induced glycoprotein hormone, has emerged as a potential biochemical marker of fetal oxygenation. Aim: This study aimed to evaluate amniotic fluid and umbilical cord serum EPO levels as biomarkers of fetal hypoxia in term and prolonged pregnancies and to assess their relationship with gestational age, umbilical artery pH, and labor characteristics. Methods: A hospital-based cross-sectional study was conducted at the Gynecologic and Pediatric Hospital in Kirkuk, Iraq, from January 2024 to August 2025. Forty women with singleton pregnancies undergoing planned induction of labor at ≥37 weeks were enrolled. Amniotic fluid and umbilical cord blood samples were collected at delivery and analyzed for EPO using enzyme-linked immunosorbent assay (ELISA). Umbilical artery pH was measured using the Epoc Blood Analysis System. Maternal, obstetric, and neonatal data were recorded. Statistical analysis included independent t-tests, Chi-square tests, and Pearson correlation coefficients. Results: The mean maternal age was 30.8±4.6 years, and mean BMI was 26.2±4.4 kg/m². Prolonged pregnancy was observed in 55.0% of participants. Amniotic fluid EPO levels were significantly higher in prolonged pregnancies compared with term pregnancies (5.12±1.28 vs. 3.45±0.68 IU/L, P = 0.0001). Similarly, umbilical cord serum EPO levels were markedly elevated in prolonged pregnancies (58.40±14.95 vs. 32.60±6.20 IU/L, P = 0.0001). A strong positive correlation was observed between amniotic fluid EPO and gestational age (r = 0.67, P < 0.001), and between cord serum EPO and gestational age (r = 0.64, P < 0.001). Amniotic fluid and cord serum EPO levels were also significantly correlated (r = 0.59, P < 0.001). Umbilical artery pH was significantly lower in prolonged pregnancies (7.24±0.05 vs. 7.30±0.04, P = 0.02), and labor duration was significantly longer (405±22.4 vs. 285±16.8 minutes, P = 0.001). Conclusion: Amniotic fluid and umbilical cord serum erythropoietin levels increase significantly with advancing gestational age and are associated with reduced umbilical artery pH and prolonged labor. These findings indicate that EPO is a sensitive biomarker of fetal hypoxic stress in late-term and prolonged pregnancies. Combined assessment of EPO and conventional fetal monitoring may improve risk stratification and support timely obstetric intervention.