Maternal urinary biomarkers are often used to assess fetal exposure to phenols and their precursors. Their effectiveness as a measure of exposure in epidemiological studies depends on their ...variability during pregnancy and their ability to accurately predict fetal exposure.
We assessed the relationship between urinary and amniotic fluid concentrations of nine environmental phenols, and the reproducibility of urinary concentrations, among pregnant women.
Seventy-one women referred for amniocentesis were included. Maternal urine was collected at the time of the amniocentesis appointment and on two subsequent occasions. Urine and amniotic fluid were analyzed for 2,4- and 2,5-dichlorophenols, bisphenol A, benzophenone-3, triclosan, and methyl-, ethyl-, propyl-, and butylparabens using online solid phase extraction-high performance liquid chromatography-isotope dilution tandem mass spectrometry.
Only benzophenone-3 and propylparaben were detectable in more than half of the amniotic fluid samples; for these phenols, concentrations in amniotic fluid and maternal urine collected on the same day were positively correlated (ρ = 0.53 and 0.32, respectively). Other phenols were detected infrequently in amniotic fluid (e.g., bisphenol A was detected in only two samples). The intraclass correlation coefficients (ICCs) of urinary concentrations in samples from individual women ranged from 0.48 and 0.62 for all phenols except bisphenol A (ICC = 0.11).
Amniotic fluid detection frequencies for most phenols were low. The reproducibility of urine measures was poor for bisphenol A, but good for the other phenols. Although a single sample may provide a reasonable estimate of exposure for some phenols, collecting multiple urine samples during pregnancy is an option to reduce exposure measurement error in studies regarding the effects of phenol prenatal exposure on health.
•We investigated associations between prenatal pyrethroids and childhood behavior.•3-PBA was associated with worse internalizing behaviors and behavioral regulation.•cis-DCCA was associated with ...worse externalizing behavior and behavioral regulation.
Several previous studies of pyrethroid biomarkers and behavior have reported associations between concurrent pyrethroid levels and adverse behavioral problems in children. One geospatial study reported associations between prenatal exposure to pyrethroids and autism. However, the association between prenatal pyrethroid biomarkers and childhood behavior is unknown. The Mount Sinai Children’s Environmental Health Center is a prospective birth cohort with urinary pyrethroid biomarkers during pregnancy and behavioral measurements at 4, 6, and 7–9 years of age. Primiparous women were enrolled between 1998 and 2002. 162 mother/child pairs with complete exposure and behavioral outcomes data were used to investigate associations between detectable levels of prenatal pyrethroid metabolites and scores on the Behavioral Assessment System for Children and the Behavior Rating Inventory of Executive Function. Overall, detection frequencies of pyrethroid metabolites were low (<30%). In longitudinal mixed models, detectable levels of 3-PBA during pregnancy were associated with worse Internalizing (β −4.50, 95% CI −8.05, −0.95), Depression (β −3.21, 95% CI −6.38, −0.05), Somatization (β −3.22, 95% CI −6.38, −0.06), Behavioral Regulation (β −3.59, 95% CI −6.97, −0.21), Emotional Control (β −3.35, 95% CI −6.58, −0.12), Shifting (β −3.42, 95% CI −6.73, −0.11), and Monitoring (β −4.08, 95% CI −7.07, −1.08) scales. Detectable levels of cis-DCCA were associated with worse Externalizing (β −4.74, 95% CI −9.37, −0.10), Conduct Problems (β −5.35, 95% CI −9.90, −0.81), Behavioral Regulation (β −6.42, 95% CI −11.39, −1.45), and Inhibitory Control (β −7.20, 95% CI −12.00, −2.39). Although detection frequencies of pyrethroid metabolites were low, we found suggestive evidence that prenatal exposure to 3-PBA and cis-DCCA may be associated with a variety of behavioral and executive functioning deficits.
Perfluoroalkyl and polyfluoroalkyl substances (PFAS) are immunotoxic in laboratory studies. Human studies of immune effects are inconsistent. Using the US National Health and Nutrition Examination ...Survey (NHANES), we examined PFAS serum concentration and indicators of prevalent immune function among 12-19-y-old children.
In this cross-sectional study, we examined PFAS serum concentration in relation to measles, mumps, and rubella antibody concentrations in NHANES 1999-2000 and 2003-2004 (n = 1,191) and to allergic conditions and allergic sensitization in NHANES 2005-2006 (n = 640).
In adjusted, survey-weighted models, a doubling of perfluorooctane sulfonate (PFOS) concentration among seropositive children was associated with a 13.3% (95% confidence interval (CI): -19.9, -6.2) decrease in rubella antibody concentration and a 5.9% decrease in mumps antibody concentration (95% CI: -9.9, -1.6). We observed no adverse association between exposure and current allergic conditions, including asthma. Children with higher PFOS concentration were less likely to be sensitized to any allergen (odds ratio (OR): 0.74; 95% CI: 0.58, 0.95).
Increased exposure to several PFAS was associated with lower levels to mumps and rubella antibody concentrations, especially among seropositive individuals. These lower antibody concentrations may indicate a less robust response to vaccination or greater waning of vaccine-derived immunity over time.
Background: Prenatal exposure to organophosphate pesticides has been shown to negatively affect child neurobehavioral development. Paraoxonase 1 (PON1) is a key enzyme in the metabolism of ...organophosphates. Objective: We examined the relationship between biomarkers of organophosphate exposure, PON1, and cognitive development at ages 12 and 24 months and 6—9 years. Methods: The Mount Sinai Children's Environmental Health Study enrolled a multiethnic prenatal population in New York City between 1998 and 2002 (n = 404). Third-trimester maternal urine samples were collected and analyzed for organophosphate metabolites (w = 360). Prenatal maternal blood was analyzed for PONI activity and genotype. Children returned for neurodevelopment assessments ages 12 months (n = 200), 24 months (n = 276), and 6-9 (n = 169) years of age. Results: Prenatal total dialkylphosphate metabolite level was associated with a decrement in mental development at 12 months among blacks and Hispanics. These associations appeared to be enhanced among children of mothers who carried the PON1 Q192R QR/RR genotype. In later childhood, increasing prenatal total dialkyl-and dimethylphosphate metabolites were associated with decrements in perceptual reasoning in the maternal PON1 Q192R QQ genotype, which imparts slow catalytic activity for chlorpyrifos oxon, with a monotonie trend consistent with greater decrements with increasing prenatal exposure. Conclusion: Our findings suggest that prenatal exposure to organophosphates is negatively associated with cognitive development, particularly perceptual reasoning, with evidence of effects beginning at 12 months and continuing through early childhood. PON1 may be an important susceptibility factor for these deleterious effects.
Environmental phenols, compounds used widely in personal care and consumer products, are known endocrine disruptors. Few epidemiologic studies have examined the association of phenol biomarkers with ...breast cancer incidence and, to our knowledge, none have considered associations with mortality following breast cancer. We examined seven urinary phenol biomarkers in association with breast cancer incidence and subsequent mortality, and examined effect measure modification by body mass index (BMI).
Participants included 711 women with breast cancer and 598 women without breast cancer who were interviewed for the population-based Long Island Breast Cancer Study Project. Among women with breast cancer, phenol biomarkers were quantified in spot urine samples collected on average within three months of a first diagnosis of primary in situ or invasive breast cancer in 1996–1997. Women with breast cancer were monitored for vital status using the National Death Index. After a median follow-up of 17.6 years, we identified 271 deaths, including 98 deaths from breast cancer. We examined creatinine-corrected phenol concentrations and the sum of parabens (Σparabens) in association with breast cancer incidence using logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs), and with mortality using Cox regression to estimate hazard ratios (HRs) and 95% CIs. We evaluated multiplicative effect measure modification using cross-product terms in nested models.
The highest (vs lowest) quintiles of urinary methylparaben, propylparaben, and Σparabens were associated with risk of breast cancer with ORs ranging from 1.31 to 1.50. Methylparaben, propylparaben, and Σparabens were also associated with all-cause mortality HRs ranging from 0.68 to 0.77. Associations for breast cancer incidence were more pronounced among women with BMI < 25.0 kg/m2 than among women with BMI ≥ 25.0 kg/m2; however, associations for mortality were more pronounced among women with BMI ≥ 25 kg/m2 than among women with BMI < 25 kg/m2.
Select parabens may have differential associations with risk of developing breast cancer and mortality following breast cancer.
•Select parabens were associated with 30–50% higher odds of breast cancer•BC incidence associations were more pronounced among women with low versus high BMI•Select parabens were inversely associated with all-cause mortality•Mortality associations were more pronounced among women with high versus low BMI
There is growing evidence of pubertal maturation occurring at earlier ages, with many studies based on cross-sectional observations. This study examined age at onset of breast development ...(thelarche), and the impact of BMI and race/ethnicity, in the 3 puberty study sites of the Breast Cancer and the Environment Research Program, a prospective cohort of >1200 girls.
Girls, 6 to 8 years at enrollment, were followed longitudinally at regular intervals from 2004 to 2011 in 3 geographic areas: the San Francisco Bay Area, Greater Cincinnati, and New York City. Sexual maturity assessment using Tanner staging was conducted by using standardized observation and palpation methods by trained and certified staff. Kaplan-Meier analyses were used to describe age at onset of breast maturation by covariates.
The age at onset of breast stage 2 varied by race/ethnicity, BMI at baseline, and site. Median age at onset of breast stage 2 was 8.8, 9.3, 9.7, and 9.7 years for African American, Hispanic, white non-Hispanic, and Asian participants, respectively. Girls with greater BMI reached breast stage 2 at younger ages. Age-specific and standardized prevalence of breast maturation was contrasted to observations in 2 large cross-sectional studies conducted 10 to 20 years earlier (Pediatric Research in Office Settings and National Health and Nutrition Examination Survey III) and found to have occurred earlier among white, non-Hispanic, but not African American girls.
We observed the onset of thelarche at younger ages than previously documented, with important differences associated with race/ethnicity and BMI, confirming and extending patterns seen previously. These findings are consistent with temporal changes in BMI.
Background: Many phthalates and phenols are hormonally active and are suspected to alter the course of development. Objective: We investigated prenatal exposures to phthalate and phenol metabolites ...and their associations with body size measures of the infants at birth. Methods: We measured 5 phenol and 10 phthalate urinary metabolites in a multiethnic cohort of 404 women in New York City during their third trimester of pregnancy and recorded size of infants at birth. Results: Median urinary concentrations were > 10 μg/L for 2 of 5 phenols and 6 of 10 phthalate monoester metabolites. Concentrations of low-molecular-weight phthalate monoesters (low-MWP) were approximately 5-fold greater than those of high-molecular-weight metabolites. Low-MWP metabolites had a positive association with gestational age 0.97 day gestational age per ln-biomarker; 95% confidence interval (CI), 0.07-1.9 days, multivariate adjusted and with head circumference. Higher prenatal exposures to 2,5-dichlorophenol (2,5-DCP) predicted lower birth weight in boys (-210 g average birth weight difference between the third tertile and first tertile of 2,5-DCP; 95% CI, 71-348 g). Higher maternal benzophenone-3 (BP3) concentrations were associated with a similar decrease in birth weight among girls but with greater birth weight in boys. Conclusions: We observed a range of phthalate and phenol exposures during pregnancy in our population, but few were associated with birth size. The association of 2,5-DCP and BP3 with reduced or increased birth weight could be important in very early or small-size births. In addition, positive associations of urinary metabolites with some outcomes may be attributable partly to unresolved confounding with maternal anthropometric factors.
Background: Previous studies of DDT and breast cancer assessed exposure later in life when the breast may not have been vulnerable, after most DDT had been eliminated, and after DDT had been banned. ...Objectives: We investigated whether DDT exposure in young women during the period of peak DDT use predicts breast cancer. Methods: We conducted a prospective, nested case-control study with a median time to diagnosis of 17 years using blood samples obtained from young women during 1959-1967. Subjects were members of the Child Health and Development Studies, Oakland, California, who provided blood samples 1-3 days after giving birth (mean age, 26 years). Cases (n = 129) developed breast cancer before the age of 50 years. Controls (n = 129) were matched to cases on birth year. Serum was assayed for p,p'-DDT, the active ingredient of DDT; o,p'-DDT, a low concentration contaminant; and p,p'-DDE, the most abundant p,p'-DDT metabolite. Results: High levels of serum p,p'-DDT predicted a statistically significant 5-fold increased risk of breast cancer among women who were born after 1931. These women were under 14 years of age in 1945, when DDT came into widespread use, and mostly under 20 years as DDT use peaked. Women who were not exposed to p,p'-DDT before 14 years of age showed no association between p,p'-DDT and breast cancer (p = 0.02 for difference by age). Conclusions: Exposure to p,p'-DDT early in life may increase breast cancer risk. Many U.S. women heavily exposed to DDT in childhood have not yet reached 50 years of age. The public health significance of DDT exposure in early life may be large.
Evidence suggests prenatal phthalate exposures may have neurodevelopmental consequences. Our objective was to investigate prenatal exposure to phthalates and cognitive development in a cohort of ...young urban children.
We recruited pregnant women in New York City from 1998 to 2002 and measured concentrations of nine phthalate metabolites in urine collected in late pregnancy. We administered a neurodevelopmental screening instrument, the Bayley Scales of Infant Development II (BSID-II), to children who returned for follow-up at approximately 24 months (n=276). We estimated associations between phthalate metabolite concentrations in maternal urine and BSID-II indices (Mental Development Index (MDI), Psychomotor Development Index (PDI)).
We observed no associations between phthalate metabolite concentrations and performance on the MDI or PDI in boys and girls combined. We did, however, observe evidence of effect measure modification by sex. We observed several negative associations between metabolite concentrations and both MDI and PDI scores among girls, suggesting poorer performance across multiple metabolites, with estimates equal to a 2–3 point decrease in score per ln-unit increase in creatinine-standardized metabolite concentration. Conversely, we observed multiple weakly positive associations among boys, equal to a 1–2 point increase in score per ln-unit increase in metabolite concentration. The strongest associations were for the metabolites mono-n-butyl phthalate, mono-isobutyl phthalate, monobenzyl phthalate, and mono(3-carboxylpropyl) phthalate (MCPP).
Girls of mothers with higher urinary concentrations of MCPP and metabolites of dibutyl phthalates had lower MDI scores on the BSID-II. These same biomarker concentrations were often associated with improved scores among boys. We observed similar results for MnBP, MCPP, and MBzP on the PDI. Given the prevalence of phthalate exposures in reproductive aged women, the implications of potential neurotoxicity warrant further investigation.
•Prenatal phthalate exposure was associated with worse mental development in girls.•Strongest associations were found for metabolites of dibutyl phthalates, MBZP and MCPP.•Weak positive associations were observed among boys.
The objective of this study was to describe the assessment methods and maturation status for a multisite cohort of girls at baseline recruitment and at ages 7 and 8 years.
The method for pubertal ...maturation staging was developed collaboratively across 3 sites. Girls at ages 6 to 8 years were recruited at 3 sites: East Harlem, New York; greater Cincinnati metropolitan area; and San Francisco Bay area, California. Baseline characteristics were obtained through interviews with caregivers and anthropometric measurements by trained examiners; breast stage 2 was defined as onset of pubertal maturation. The kappa statistic was used to evaluate agreement between master trainers and examiners. Logistic regression models were used to identify factors that are associated with pubertal maturation and linear regression models to examine factors that are associated with height velocity.
The baseline cohort included 1239 girls. The proportion of girls who had attained breast stage 2 varied by age, race/ethnicity, BMI percentile, and site. At 7 years, 10.4% of white, 23.4% of black non-Hispanic, and 14.9% of Hispanic girls had attained breast stage>or=2; at 8 years, 18.3%, 42.9%, and 30.9%, respectively, had attained breast stage>or=2. The prime determinant of height velocity was pubertal status.
In this multisite study, there was substantial agreement regarding pubertal staging between examiners across sites. The proportion of girls who had breast development at ages 7 and 8 years, particularly among white girls, is greater than that reported from studies of girls who were born 10 to 30 years earlier.
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