Impact of exposure to phenols during early pregnancy on birth weight in two Canadian cohort studies subject to measurement errors.

It is of interest to know whether early pregnancy exposure to phenols such as bisphenol-A (BPA) or triclosan (TCS) negatively impacts birth weight outcomes. Exposure to these chemicals is widespread in the Canadian population but obtaining accurate measurements of average exposure is difficult because these chemicals are rapidly excreted from the body, causing body levels to fluctuate both within and between days, as observed in a recent Canadian study (P4). This measurement error can attenuate the estimated effects of exposures. Data from two Canadian cohort studies, the Plastics and Personal-care Products use in Pregnancy (P4) Study and the Maternal-Infant Research on Environmental Chemicals (MIREC) Study, such that all participants with complete BPA or TCS exposure and outcome data were used (MIREC n = 1822, P4 n = 68). We used regression calibration to correct for the attenuating effects of exposure measurement error when modeling the effect of first trimester BPA or TCS exposure on four birth weight outcomes: birth weight (BW), low birth weight (LBW), small for gestational age (SGA) and large for gestational age (LGA). Specific gravity, time of day, and time since last urine void were also controlled in the analysis. TCS exposure has a marginally significant association with SGA only with odds ratio 0.87 and 95% confidence interval (0.74, 1.00). It also has a marginally significant association with LGA in male offspring with odds ratio 1.11 and 95% confidence interval (1.00, 1.25). The effects of BPA on the four birth outcomes were insignificant. Increased TCS exposure during pregnancy is marginally associated with decreased odds of having SGA offspring. It is possibly associated with decreased BW in males and decreased odds of LBW, though these associations were not present in measurement error corrected models. TCS is possibly associated with increased odds in male offspring of being LGA, though this relationship was not present in models not corrected for measurement error. The study finds no significant effects of BPA on birth weight outcomes, which may be due to more severe measurement error in a single observation of BPA.

Lester F ，Arbuckle TE ，Peng Y ，McIsaac MA ... -  《-》

Prenatal exposure to phthalates and phenols and infant endocrine-sensitive outcomes: The MIREC study.

Anogenital distance (AGD) and the second to fourth finger (2D:4D) digit ratio may be early markers of in utero androgen exposure for the infant. Phthalates and phenols have been identified as endocrine disrupting chemicals. To study the association between prenatal exposure to phthalates, bisphenol A (BPA) and triclosan (TCS) and AGD and the 2D:4D digit ratios. Single spot urine samples were collected in the first trimester from the MIREC Study and analyzed for phthalates and phenols. Anogenital distance (n = 394) at birth and 2D:4D digit ratios (n = 420) at 6 months were measured in male and female infants. Associations between maternal concentrations of phenols and phthalate metabolites and these outcomes were estimated using multiple linear regression models. In females, the anoclitoris distance (ACD) was negatively associated with mono-benzyl phthalate (MBzP) (β = -1.24; 95% CI -1.91, -0.57) and positively associated with mono-ethyl phthalate (MEP) (β = 0.65; 95% CI 0.12, 1.18) (masculinizing). In males, anopenile distance (APD) was positively associated with mono-n-butyl phthalate (MnBP) (β = 1.17; 95% CI 0.02, 2.32) and the molar sum of low molecular weight phthalates (ΣLMW). Female 2D:4D of the right hand was positively associated with MnBP and negatively with total BPA (masculinizing). Significant associations were only observed for the long AGD metrics. Positive associations were observed between MnBP or LMW phthalates and APD in males. In females, prenatal MEP was associated with a masculinizing effect on ACD, while MBzP was associated with a feminizing effect. No significant associations were observed between prenatal phenols and AGD. Given the paucity of research on digit ratios and prenatal chemical exposures, it is difficult to say whether this metric will be a useful marker of prenatal androgen or anti-androgen exposure. Given the large number of associations examined, the statistical associations observed may have been due to Type 1 error. The inconsistencies in results between studies suggest that this issue is yet to be resolved.

Arbuckle TE ，Agarwal A ，MacPherson SH ，Fraser WD ，Sathyanarayana S ，Ramsay T ，Dodds L ，Muckle G ，Fisher M ，Foster W ，Walker M ，Monnier P ... -  《-》

Exposure to free and conjugated forms of bisphenol A and triclosan among pregnant women in the MIREC cohort.

Arbuckle TE ，Marro L ，Davis K ，Fisher M ，Ayotte P ，Bélanger P ，Dumas P ，LeBlanc A ，Bérubé R ，Gaudreau É ，Provencher G ，Faustman EM ，Vigoren E ，Ettinger AS ，Dellarco M ，MacPherson S ，Fraser WD ... -  《-》

Associations between Maternal Exposure to Bisphenol A or Triclosan and Gestational Hypertension and Preeclampsia: The MIREC Study.

Little is known about the association between bisphenol A (BPA) or triclosan (TCS) exposure and hypertension in pregnancy. To investigate potential associations between maternal urinary concentrations of BPA or TCS and gestational hypertension (GH) and preeclampsia. Among 1,909 pregnant women participating in the maternal-infant research on environmental chemicals (MIREC) study, urinary concentrations of BPA and TCS were measured in the first trimester by liquid chromatography-tandem mass spectrometry using isotope dilution. Blood pressure was measured during each trimester. Multinomial regression was performed to estimate the adjusted odds ratio (aOR) and 95% confidence intervals (CI) for the associations between these phenols and GH and preeclampsia. BPA and TCS were not associated with GH or preeclampsia. However, in multiparous women, BPA (0.50-1.30 µg/L) was associated with decreased risk of GH (aOR =0.45; 95%CI: 0.21-0.98) while among nulliparous women, TCS was associated with an increased risk of GH (3.60-32.60 µg/L; aOR = 2.58; 95% CI: 1.09-6.13 and > 32.60 µg/L: aOR = 2.74; 95% CI: 1.15-6.51). BPA and TCS urinary concentrations were not associated with GH or preeclampsia; however, our results suggest an association between TCS and GH in nulliparous women. Additional studies are required to confirm our results.

Camara LR ，Arbuckle TE ，Trottier H ，Fraser WD ... -  《-》

Bisphenol A and other phenols in urine from Danish children and adolescents analyzed by isotope diluted TurboFlow-LC-MS/MS.

Bisphenol A (BPA), triclosan (TCS), benzophenone-3 (BP-3), dichoro- and phenyl phenols are industrial chemicals present in numerous consumer products such as polycarbonate plastics, preservatives in personal care products, sun screens, pesticides and fungicides, respectively, and they are all suspected endocrine disrupters. In this study the urinary excretion of eight phenols in Danish children recruited from the general population were investigated. One 24h urine and two consecutive first morning samples were collected from each of 129 healthy Danish children and adolescents (6-21 years). The concentrations of urinary phenols were analyzed by a new on-line TurboFlow-liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. Most of the analyzed phenols were detectable in more than 80% of the 24h urine samples and the median concentration of BPA, TCS, BP-3, 2,4-dichorophenol and 2,5-dichorophenol (analyzed as ∑DCP), 2-phenylphenol and 4-phenylphenol were 1.37, 1.45, 1.41, 0.65, 0.36 and 0.53ng/mL, respectively. The ranges of the excreted TCS and BP-3 were wide; from below limit of detection to maximum levels of 955ng/mL and 162ng/mL, respectively, while the other phenols were excreted in a more narrow range with maximum levels below 25ng/mL. Concentrations in first morning urine were in general higher than in 24h urine and comprised 30-47% of the absolute amount excreted during 24h. The youngest children aged 6-10 years had a significantly higher urinary BPA concentration (ng/mL) and also a relatively higher daily BPA excretion (ng/kg bw/24h) than the older children and adolescents. The opposite pattern was observed for TCS, BP-3 and ∑DCP for which urinary levels increased significantly with age. No gender difference or associations to pubertal development were observed. In conclusion, our study showed that Danish children were exposed to multiple phenols simultaneously. Small children were relatively more exposed to BPA than older children, while higher exposures to TCS, BP-3 and ∑DCP were seen among adolescents.

Frederiksen H ，Aksglaede L ，Sorensen K ，Nielsen O ，Main KM ，Skakkebaek NE ，Juul A ，Andersson AM ... -  《-》