Associations of fetal growth outcomes with measures of the combined xenoestrogenic activity of maternal serum perfluorinated alkyl acids in Danish pregnant women

TY - JOUR

T1 - Associations of fetal growth outcomes with measures of the combined xenoestrogenic activity of maternal serum perfluorinated alkyl acids in Danish pregnant women

AU - Olesen, Christian Bjerregaard

AU - Bach, Cathrine Carlsen

AU - Long, Manhai

AU - Wielsøe, Maria

AU - Bech, Bodil Hammer

AU - Henriksen, Tine Brink

AU - Olsen, Jørn

AU - Bonefeld-Jørgensen, Eva Cecilie

PY - 2019/1/24

Y1 - 2019/1/24

N2 - 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 (CI): -90, -6] 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 xenoestrogenic activities were associated with lower BW and length in offspring, suggesting that PFAA mixtures may affect fetal growth by disrupting ER function.

AB - 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 (CI): -90, -6] 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 xenoestrogenic activities were associated with lower BW and length in offspring, suggesting that PFAA mixtures may affect fetal growth by disrupting ER function.

KW - Adult

KW - Birth Weight/drug effects

KW - Body Size/drug effects

KW - Cell Line, Tumor

KW - Cohort Studies

KW - Denmark/epidemiology

KW - Endocrine Disruptors/adverse effects

KW - Female

KW - Fetal Development/drug effects

KW - Fluorocarbons/adverse effects

KW - Head/growth & development

KW - Humans

KW - Infant, Newborn

KW - Male

KW - Pregnancy/blood

KW - Prenatal Exposure Delayed Effects

KW - Receptors, Estrogen/metabolism

KW - Transcriptional Activation

KW - Transfection

UR - http://www.scopus.com/inward/record.url?scp=85060380560&partnerID=8YFLogxK

U2 - 10.1289/EHP1884

DO - 10.1289/EHP1884

M3 - Journal article

C2 - 30676078

SN - 0091-6765

VL - 127

JO - Environmental Health Perspectives

JF - Environmental Health Perspectives

IS - 1

M1 - 17006

ER -