Associations of Fetal Growth Outcomes with Measures of the Combined Xenoestrogenic Activity of Maternal Serum Perfluorinated Alkyl Acids in Danish Pregnant Women

BACKGROUND: Higher concentrations of single perfluorinated alkyl acids (PFAAs) have been associated with lower birth weight (BW), but few studies have examined the combined effects of PFAA mixtures. PFAAs have been reported to induce estrogen receptor (ER) transactivity, and estrogens may influence human fetal growth. We hypothesize that mixtures of PFAAs may affect human fetal growth by disrupting the ER. OBJECTIVES: We aimed to study the associations between the combined xenoestrogenic activity of PFAAs in pregnant women's serum and offspring BW, length, and head circumference. METHODS: We extracted the actual mixture of PFAAs from the serum of 702 Danish pregnant women (gestational wk 11-13) enrolled in the Aarhus Birth Cohort (ABC) using solid phase extraction, high-performance liquid chromatography (HPLC), and weak anion exchange. PFAA-induced xenoestrogenic receptor transactivation (XER) was determined using the stable transfected MVLN cell line. Associations between XER and measures of fetal growth were estimated using multivariable linear regression with primary adjustment for maternal age, body mass index (BMI), educational level, smoking, and alcohol intake, and sensitivity analyses with additional adjustment for gestational age (GA) (linear and quadratic). RESULTS: On average, an interquartile range (IQR) increase in XER was associated with a 48 g [95% confidence interval (CO: 90, 61 decrease in BW and a 0.3 cm (95% CI: 0.1, 0.5) decrease in birth length. Upon additional adjustment for GA, the estimated mean differences were 28 g (95% CI: 60, 4) and -0.2 cm (95% CI: -0.4, 0.0), respectively. CONCLUSION: Higher-serum PFAA-induced xenocstrogenic activities were associated with lower BW and length in offspring, suggesting that PFAA mixtures may affect fetal growth by disrupting ER function.