Association of phthalate exposure during early pregnancy with fetal growth and the effect modification by gestational stress.

Nan-Lin Wu, Zhi Bi Hu, Xiao-He Xiao, Shengdao Xiong, X J Liu, Yi-Cheng Xie, Rong Zeng, Kang Tian, X Shen, Yun-fen Zhou, Yen-Ni Liu

Int J Hyg Environ Health

May 31, 2026

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Abstract

AIMS: To analyze the association between first-trimester phthalates (PAEs) exposure and fetal growth, and explore the potential effect modification of first-trimester pregnancy stress on this association. METHODS: We included 704 pregnant women in the first-trimester from the Zunyi birth cohort. Fetal growth parameters (biparietal diameter, head circumference (HC), abdominal circumference (AC), femur length (FL), estimated fetal weight (EFW), placental thickness (PT)) were assessed via ultrasonography. Urinary concentrations of nine PAE metabolites were quantified using gas chromatography-tandem mass spectrometry，and pregnancy stress was self-reported. Linear regression analyzed associations of individual urinary PAE metabolite, pregnancy stress, and fetal growth. Bayesian Kernel Machine Regression (BKMR) assessed PAE mixtures. Stratified analysis by stress levels and interaction terms were evaluated. RESULTS: An interquartile range (IQR) increase in MEOHP was associated with reduced HC Z-score (β = -0.037; 95% CI: -0.066, -0.008; P = 0.013) and PT (β= -0.260 mm; 95% CI: -0.490, -0.030; P = 0.027); IQR increases in MBzP and MEP were linked to decreased AC Z-score (β = -0.060; 95% CI: -0.099, -0.021; P = 0.003) and FL Z-score (β = -0.070; 95% CI: -0.116, -0.023; P = 0.003), respectively. BKMR models indicated that total PAE mixture concentrations above the 60th percentile were significantly associated with lower FL Z-scores. Gestational stress was associated with reduced PT (1-2 stressors:β= -0.801 mm; 95% CI: -1.442, -0.161; P = 0.014; 3 stressors:β= -1.177 mm; 95% CI: -2.102, -0.251; P = 0.013). Gestational stress significantly modified the associations of MEHHP/ΣDEHP-HC, MMP-AC, and MEP-FL (P