Fetal Growth Restriction and Maternal Serum Phthalate Levels in Pregnancy: A Case-Control Study

Abstract

OBJECTIVE: The study aimed to investigate the association between maternal serum di-2-ethylhexyl phthalate (DEHP) levels-DEHP is a chemical widely used in plastics, as well as in the food and cosmetics industries-and fetal growth restriction (FGR, a condition where the fetus fails to achieve expected growth).

STUDY DESIGN: This study included 84 women between April and July 2019: 40 with fetal growth restriction and 44 gestational age-matched controls. Maternal plasma levels of DEHP were measured with sensitive, specific immunoassays and with Ultra Performance Liquid Chromatography-Mass Spectrometry (UPLC-MS).

RESULTS: Patient ages ranged from 18 to 40 years (mean 27.16±5.70). Age, BMI, and smoking distributions did not differ significantly between groups (p>0.05). Serum DEHP levels were significantly higher in the FGR (+) group than in the FGR (−) group (p=0.001; p<0.01). Based on this, we calculated a serum DEHP cut-off using ROC analysis and diagnostic screening. The area under the ROC curve was 0.693 [95% CI: 0.580–0.807; p=0.002; p<0.01]. At a cut-off >107.93, sensitivity was 70.0%, specificity 68.2%, PPV 66.7%, NPV 71.4%, accuracy 69.1%, and Youden index 0.382.

CONCLUSION: This study demonstrates a significant association between higher maternal phthalate levels and fetal growth restriction. These findings contribute to emerging evidence linking phthalate exposure to impaired fetal development; however, maternal serum phthalate levels are not currently suitable for clinical prediction or early detection of FGR. To address these limitations, further studies with larger cohorts and longitudinal designs are needed to confirm these associations and explore underlying mechanisms.