Environmental phenol exposures in 6- to 12-week-old infants: The Infant Feeding and Early Development (IFED) study.

BACKGROUND: Exposure to phenols, endocrine-disrupting chemicals used in personal care and consumer products, is widespread. Data on infant exposures are limited despite heightened sensitivity to endocrine disruption during this developmental period. We aimed to describe distributions and predictors of urinary phenol concentrations among U.S. infants ages 6-12 weeks. METHODS: The Infant Feeding and Early Development (IFED) study is a prospective cohort study of healthy term infants enrolled during 2010-2013 in the Philadelphia region. We measured concentrations of seven phenols in 352 urine samples collected during the 6- or 8- and/or 12-week study visits from 199 infants. We used linear mixed models to estimate associations of maternal, sociodemographic, infant, and sample characteristics with natural-log transformed, creatinine-standardized phenol concentrations and present results as mean percent change from the reference level. RESULTS: Median concentrations (µg/L) were 311 for methylparaben, 10.3 for propylparaben, 3.6 for benzophenone-3, 2.1 for triclosan, 1.0 for 2,5-dichlorophenol, 0.7 for BPA, and 0.3 for 2,4-dichlorophenol. Geometric mean methylparaben concentrations were approximately 10 times higher than published estimates for U.S. children ages 3-5 and 6-11 years, while propylparaben concentrations were 3-4 times higher. Infants of Black mothers had higher concentrations of BPA (83%), methylparaben (121%), propylparaben (218%), and 2,5-dichorophenol (287%) and lower concentrations of benzophenone-3 (-77%) and triclosan (-53%) than infants of White mothers. Triclosan concentrations were higher in breastfed infants (176%) and lower in infants whose mothers had a high school education or less (-62%). Phenol concentrations were generally higher in summer samples. CONCLUSIONS: Widespread exposure to select environmental phenols among this cohort of healthy U.S. infants, including much higher paraben concentrations compared to those reported for U.S. children, supports the importance of expanding population-based biomonitoring programs to infants and toddlers. Future investigation of exposure sources is warranted to identify opportunities to minimize exposures during these sensitive periods of development.

Early Life Anti-Müllerian Hormone Trajectories in Infant Girls.

BACKGROUND: Minipuberty is a period of increased reproductive axis activity in infancy, but the importance of this period is not well understood, especially in girls. Previous studies reported a peak in hormone concentrations at 3 to 4 months old. Our objective is to describe anti-Müllerian hormone (AMH) trajectories in the context of other minipuberty factors among healthy infant girls using longitudinal measures of AMH. METHODS: The Infant Feeding and Early Development study is a longitudinal cohort study of healthy infants, recruited from hospitals in the Philadelphia area during 2010 to 2013. We measured AMH in 153 girls who contributed 1366 serum samples across 11 study visits over 36 weeks. We also measured follicle stimulating hormone (FSH), estradiol, and ovarian characteristics. We used latent class mixed effects models to cluster trajectories of AMH concentration with age. Using linear mixed models, we estimated FSH and ovarian characteristic trajectories separately by AMH cluster. RESULTS: We classified infants into four clusters that represent patterns of AMH that were high and decreasing (decreasing), had a peak around 12 weeks or 20 weeks (early peak and middle peak), or were consistently low (low). Infants in these clusters differed in their FSH trajectories, timing of estradiol production, and ovarian characteristics. CONCLUSIONS: The AMH clusters identified suggest variation in the timing and the magnitude of the minipuberty response in infant girls. The decreasing and low clusters have not been described previously and should be further evaluated to determine whether they represent an opportunity for the early identification of later reproductive conditions.

Reproductive Hormone Concentrations and Associated Anatomical Responses: Does Soy Formula Affect Minipuberty in Boys?

CONTEXT: Soy formula feeding is common in infancy and is a source of high exposure to phytoestrogens, documented to influence vaginal cytology in female infants. Its influence on minipuberty in males has not been established. OBJECTIVE: To assess the association between infant feeding practice and longitudinally measured reproductive hormones and hormone-responsive tissues in infant boys. METHODS: The Infant Feeding and Early Development study was a prospective cohort of maternal-infant dyads requiring exclusive soy formula, cow milk formula, or breast milk feeding during study follow-up. In the 147 infant boy participants, serum testosterone, luteinizing hormone, stretched penile length, anogenital distance, and testis volume were longitudinally assessed from birth to 28 weeks. We examined feeding-group differences in age trajectories for these outcomes using mixed-effects regression splines. RESULTS: Median serum testosterone was at pubertal levels at 2 weeks (176 ng/dL [quartiles: 124, 232]) and remained in this range until 12 weeks in all feeding groups. We did not observe differences in trajectories of hormone concentrations or anatomical measures between boys fed soy formula (n = 55) and boys fed cow milk formula (n = 54). Compared with breastfed boys (n = 38), soy formula-fed boys had a more rapid increase in penile length (P = .004) and slower initial lengthening of anogenital distance (P = .03), but no differences in hormone trajectories. CONCLUSION: Reproductive hormone concentrations and anatomical responses followed similar trajectories in soy and cow milk formula-fed infant boys. Our findings suggest that these measures of early male reproductive development do not respond to phytoestrogen exposure during infancy.

Characterization of ovarian development in girls from birth to 9 months.

BACKGROUND: The minipuberty of infancy is a period of increased reproductive axis activity. Changes in reproductive hormone concentrations and organ size occur during this period, but longitudinal changes have not been well described. OBJECTIVES: The objective of this study was to characterize ovarian growth trajectories and ovarian follicle development during the first 9 months of life in a large longitudinal cohort of healthy girls. METHODS: Data from the Infant Feeding and Early Development Study, a longitudinal cohort study of oestrogen-responsive outcomes in healthy infants, were used to estimate ovarian growth trajectories and describe the presence of ovarian antral follicles in girls 0-9 months old. Ovarian ultrasound evaluations were performed on the infants within 72 hours of birth (newborn visit) and at 4, 8, 16, 24, and 32 weeks of age. Mixed-effects regression splines were used to characterize changes in ovarian volume during infancy and assess the association between the presence of ovarian follicles at the newborn visit and ovarian growth. RESULTS: This analysis included 163 girls with two or more ovarian ultrasounds in the study. Results from the estimated overall ovarian growth trajectory show that ovarian volume increases more than sixfold during the first 16 weeks after birth and then remains relatively stable in the later weeks of infancy. Among girls with observable ovaries at the newborn visit (n = 133), girls with at least one visible ovarian follicle showed more rapid initial ovarian growth compared with girls without visible follicles. CONCLUSIONS: Infant ovarian volume increased to a peak at 16 weeks, which was influenced by the number and size of developing follicles. This research contributes to future development of reference ranges for postnatal ovarian growth in healthy, term infants.

Incidental findings during ultrasound of thyroid, breast, testis, uterus and ovary in healthy term neonates.

Incidental sonographic findings in thyroid and estrogen-responsive organs have been described in children and adults, but no publications describe incidental findings of these organs in infancy. We describe ultrasound features in thyroid, breast buds, testes, uterus, and ovaries in infants up to 32 weeks old that vary from the expected tissue architecture. Infants described in this paper were enrolled as healthy term neonates in a longitudinal study of normal feeding practices. Radiology reports for ultrasound exams in these infants described a range of findings that are similar to those reported in older populations. Knowledge of these asymptomatic variants occurring in infancy may guide radiologists in interpretation of these findings during clinical exams.

A Longitudinal Study of Estrogen-Responsive Tissues and Hormone Concentrations in Infants Fed Soy Formula.

Purpose: Chemicals with hormonelike activity, such as estrogenic isoflavones, may perturb human development. Infants exclusively fed soy-based formula are highly exposed to isoflavones, but their physiologic responses remain uncharacterized. Estrogen-responsive postnatal development was compared in infants exclusively fed soy formula, cow-milk formula, and breast milk. Methods: We enrolled 410 infants born in Philadelphia-area hospitals between 2010 and 2014; 283 were exclusively fed soy formula (n = 102), cow-milk formula (n = 111), or breast milk (n = 70) throughout the study (birth to 28 or 36 weeks for boys and girls, respectively). We repeatedly measured maturation index (MI) in vaginal and urethral epithelial cells using standard cytological methods, uterine volume and breast-bud diameter using ultrasound, and serum estradiol and follicle-stimulating hormone levels. We estimated MI, organ-growth, and hormone trajectories by diet using mixed-effects regression splines. Results: Maternal demographics did not differ between cow-milk-fed and soy-fed infants but did differ between formula-fed and breastfed infants. Vaginal-cell MI trended higher (P = 0.01) and uterine volume decreased more slowly (P = 0.01) in soy-fed girls compared with cow-milk-fed girls; however, their trajectories of breast-bud diameter and hormone concentrations did not differ. We observed no significant differences between boys fed cow-milk vs soy formula; estradiol was not detectable. Breastfed infants differed from soy-formula-fed infants in vaginal-cell MI, uterine volume, and girls' estradiol and boys' breast-bud diameter trajectories. Conclusions: Relative to girls fed cow-milk formula, those fed soy formula demonstrated tissue- and organ-level developmental trajectories consistent with response to exogenous estrogen exposure. Studies are needed to further evaluate the effects of soy on child development.

Soy Formula and Epigenetic Modifications: Analysis of Vaginal Epithelial Cells from Infant Girls in the IFED Study.

BACKGROUND: Early-life exposure to estrogenic compounds affects the development of the reproductive system in rodent models and humans. Soy products, which contain phytoestrogens such as genistein, are one source of exposure in infants fed soy formula, and they result in high serum concentrations. OBJECTIVES: Our goal was to determine whether soy exposure is associated with differential DNA methylation in vaginal cells from soy-fed infant girls. METHODS: Using the Illumina HumanMethylation450 BeadChip, we evaluated epigenome-wide DNA methylation in vaginal cells from four soy formula-fed and six cow formula-fed girls from the Infant Feeding and Early Development (IFED) study. Using pyrosequencing we followed up the two most differentially methylated sites in 214 vaginal cell samples serially collected between birth and 9 months of age from 50 girls (28 soy formula-fed and 22 cow formula-fed). With a mouse model, we examined the effect of neonatal exposure to genistein on gene specific mRNA levels in vaginal tissue. RESULTS: The epigenome-wide scan suggested differences in methylation between soy formula-fed and cow formula-fed infants at three CpGs in the gene proline rich 5 like (PRR5L) (p < 104). Pyrosequencing of the two feeding groups found that methylation levels progressively diverged with age, with pointwise differences becoming statistically significant after 126 days. Genistein-exposed mice showed a 50% decrease in vaginal Prr5l mRNA levels compared to controls. CONCLUSIONS: Girls fed soy formula have altered DNA methylation in vaginal cell DNA which may be associated with decreased expression of an estrogen-responsive gene. Citation: Harlid S, Adgent M, Jefferson WN, Panduri V, Umbach DM, Xu Z, Stallings VA, Williams CJ, Rogan WJ, Taylor JA. 2017. Soy formula and epigenetic modifications: analysis of vaginal epithelial cells from infant girls in the IFED study. Environ Health Perspect 125:447-452; http://dx.doi.org/10.1289/EHP428.

Size of testes, ovaries, uterus and breast buds by ultrasound in healthy full-term neonates ages 0-3 days.

BACKGROUND: Hormonally sensitive organs in the neonate can change size within days of birth as circulating maternal estrogen wanes. Although several reports document the size of these organs through infancy, few focus attention on the near-birth period. Clinical and research evaluation of hormonal and genitourinary disorders would benefit from reference size standards. OBJECTIVE: We describe the size of the uterus, ovaries, testes and breast buds in healthy term neonates. MATERIALS AND METHODS: As part of the Infant Feeding and Early Development (IFED) study, we sonographically measured the largest diameter of these organs in sagittal, transverse and anterior-posterior planes for 194 female and 204 male newborns up to 3 days old. We calculated mean, median and percentiles for longest axis length and for volume calculated from measured diameters. We evaluated size differences by laterality, gender and race and compared our observations against published values. RESULTS: Mean length and mean volume were as follows: uterus, 4.2 cm and 10.0 cm3; ovary, 1.0 cm and 0.2 cm3; testis, 1.1 cm and 0.3 cm3 (0.4 cm3 Lambert volume); female breast bud, 1.2 cm and 0.7 cm3; male breast bud, 1.1 cm and 0.6 cm3. Breast buds were larger in females than males. Laterality differences were typically below the precision of clinical measurement. No significant race differences were detected. CONCLUSION: Using data from our large cohort together with published values, we provide guidelines for evaluating the size of reproductive organs within the first 3 days of age. Discrepancies between our results and published values are likely attributable to technique.

Prenatal exposure to perfluroalkyl substances and children's IQ: The Taiwan maternal and infant cohort study.

BACKGROUND: Perfluoroalkyl substances (PFASs) are a group of fluorinated organic substances that are widely used in consumer products and are often detectable in human tissues. Human studies on prenatal exposure to PFASs and neurodevelopment in children are few and inconsistent. METHODS: In the Taiwan Maternal and Infant Cohort Study, we collected serum samples from pregnant women during the third trimester and measured concentrations of 9 PFASs using a high performance liquid chromatography system. A subsample of their children was assessed with full scale intelligence quotient (FSIQ), verbal IQ (VIQ) and performance IQ (PIQ) at both age 5 (n=120) and 8 years (n=120). We used multivariate linear regression models to examine prenatal PFAS exposure in relation to IQ scores at each age period. RESULTS: Prenatal perfluoroundecanoic acid (PFUnDA) concentrations were inversely associated with children's PIQ scores at age 5 years, with an adjusted coefficient (ß) of -1.6 (95% confidence interval [CI]: (-3.0, -0.2). When children reached 8 years, most of the prenatal PFASs showed inverse association with children's FSIQ, VIQ and PIQ scores. Among them, prenatal perfluorononanoic acid (PFNA) reached significance. Children with higher prenatal PFNA levels had lower VIQ with an adjusted ß of -2.1 (95% CI: -3.9, -0.2). CONCLUSIONS: We found two prenatal PFAS exposure, both long-chain PFASs, in association with decreased IQ test scores in children. Our findings suggest more studies on long-chain PFASs and children's neurodevelopment.

Triclosan and prescription antibiotic exposures and enterolactone production in adults.

BACKGROUND: The gut microbiome plays an important role in the development of disease. The composition of the microbiome is influenced by factors such as mode of delivery at birth, diet and antibiotic use, yet the influence of environmental chemical exposures is largely unknown. The antimicrobial compound triclosan, found in many personal care products and widely detected in human urine, is an environmental exposure for which systemic microbiotic effects may be of particular interest. To investigate the relationship between triclosan and gut microflora, we assessed the association between triclosan and enterolactone, an intestinal metabolite that is produced via bacterial transformation of dietary lignans (seeds, nuts) and has known susceptibility to oral antibiotics. METHODS: We examined urinary triclosan and enterolactone for 2005-2008 U.S. National Health and Nutrition Examination Survey subjects, aged ≥20 years (n=3041). We also examined the association between prescription antibiotic use and enterolactone to confirm its susceptibility to changes in bacterial composition of the body. Associations between natural log-transformed enterolactone and (1) detected vs. not detected (<2.3 ng/mL) triclosan, (2) triclosan quintiles (Q1-Q5), and (3) any vs. no antibiotics were estimated with multiple linear regression, adjusting for sex, age, race, body mass index, poverty income ratio, education, fiber intake, bowel movement frequency, cotinine and creatinine (n=2441). RESULTS: Triclosan was detected in 80% of subjects (range: <2.3-3620 ng/mL), while enterolactone was detected in >99% of subjects (range: <0.1-122,000 ng/mL). After adjustment, enterolactone was not associated with triclosan (detect vs. non-detect: ß= 0.07 (95% CI: -0.15, 0.30); Q5 (≥104.5 ng/mL) vs. Q1 (none): ß= 0.06 (95% CI: -0.21, 0.34)). In sex-stratified analyses, triclosan was associated with higher enterolactone in women (detect vs. non-detect: ß= 0.31 (95% CI: -0.07, 0.70), but not men ß= -0.18 (95% CI: -0.47, 0.11). However, any antibiotic use (n=112), as compared to no antibiotic use, was associated with significantly lower enterolactone (ß=-0.78 (95%CI: -1.22, -0.36)), with no sex-specific effects. This association was driven by inverse associations with the following antibiotic classes: macrolide derivatives, quinolones, sulfonamides, and lincomycin derivatives. CONCLUSIONS: Antibiotics, but not triclosan, are negatively associated with urinary enterolactone. Antibiotics may reduce enterolactone by killing certain gut bacteria. At levels detected in the U.S., triclosan does not appear to be acting similarly, despite broad antimicrobial properties. Additional study of determinants of triclosan exposure and enterolactone production may be needed to better understand positive associations among women.

Recreational Exercise Before and During Pregnancy in Relation to Plasma C-Reactive Protein Concentrations in Pregnant Women.

BACKGROUND: Pregnant women who are physically active have a lower risk of preeclampsia and gestational diabetes than women who are less active. One possible mechanism is a reduction in low-grade inflammation, as measured by plasma concentrations of C-reactive protein (CRP). The association between exercise and CRP in pregnant women, however, has not been adequately investigated. METHODS: A total of 537 pregnant women, enrolled around the 17th week of gestation in the Norwegian Mother and Child Cohort Study in 2003 to 2004, were studied. Self-reported recreational exercise was recalled for both 3 months before pregnancy and early pregnancy. The total energy expenditure from recreational exercise (total recreational exercise, metabolic equivalent of task [MET]-hr/week) was estimated, and low-, moderate- and vigorous-intensity exercise was defined. Plasma CRP concentrations were measured during pregnancy. RESULTS: In adjusted linear regression models, mean CRP concentration was 1.0% lower [95% CI = -1.9% to 0.2%] with each 1 MET-hr/week of total recreational exercise before pregnancy. In addition, vigorous-intensity exercise before pregnancy was more strongly related to a reduction in CRP levels than low- or moderate-intensity exercise. However, we observed no association between recreational exercise during pregnancy and plasma CRP levels. CONCLUSIONS: Recreational exercise before pregnancy, especially vigorous exercise, may reduce the risk of maternal inflammation during pregnancy.

Blood lead concentrations and children's behavioral and emotional problems: a cohort study.

IMPORTANCE: The association between lead exposure and children's IQ has been well studied, but few studies have examined the effects of blood lead concentrations on children's behavior. OBJECTIVE: To evaluate the association between blood lead concentrations and behavioral problems in a community sample of Chinese preschool children with a mean blood lead concentration of less than 10 µg/dL. DESIGN, SETTING, AND PARTICIPANTS: A prospective cohort study was conducted at 4 preschools in Jintan, Jiangsu province of China. Participants included 1341 children aged 3 to 5 years. EXPOSURES: Lead. MAIN OUTCOMES AND MEASURES: Blood lead concentrations were measured in children aged 3 to 5 years. Behavioral problems were assessed using Chinese versions of the Child Behavior Checklist and Caregiver-Teacher Report Form when children were aged 6 years. RESULTS: The mean (SD) blood lead concentration was 6.4 (2.6) µg/dL, with the 75th and 90th percentiles being 7.5 and 9.4 µg/dL, respectively. General linear modeling showed significant associations between blood lead concentrations and increased scores for teacher-reported behavioral problems. A 1-µg/dL increase in the blood lead concentration resulted in a 0.322 (95% CI, 0.058 to 0.587), 0.253 (95% CI, 0.016 to 0.500), and 0.303 (95% CI, 0.046 to 0.560) increase of teacher-reported behavior scores on emotional reactivity, anxiety problems, and pervasive developmental problems, respectively (P < .05), with adjustment for parental and child variables. Spline modeling showed that mean teacher-reported behavior scores increased with blood lead concentrations, particularly for older girls. CONCLUSIONS AND RELEVANCE: Blood lead concentrations, even at a mean concentration of 6.4 µg/dL, were associated with increased risk of behavioral problems in Chinese preschool children, including internalizing and pervasive developmental problems. This association showed different patterns depending on age and sex. As such, continued monitoring of blood lead concentrations, as well as clinical assessments of mental behavior during regular pediatric visits, may be warranted.

Iodine deficiency, pollutant chemicals, and the thyroid: new information on an old problem.

Many women of reproductive age in the United States are marginally iodine deficient, perhaps because the salt in processed foods is not iodized. Iodine deficiency, per se, can interfere with normal brain development in their offspring; in addition, it increases vulnerability to the effects of certain environmental pollutants, such as nitrate, thiocyanate, and perchlorate. Although pregnant and lactating women should take a supplement containing adequate iodide, only about 15% do so. Such supplements, however, may not contain enough iodide and may not be labeled accurately. The American Thyroid Association recommends that pregnant and lactating women take a supplement with adequate iodide. The American Academy of Pediatrics recommends that pregnant and lactating women also avoid exposure to excess nitrate, which would usually occur from contaminated well water, and thiocyanate, which is in cigarette smoke. Perchlorate is currently a candidate for regulation as a water pollutant. The Environmental Protection Agency should proceed with appropriate regulation, and the Food and Drug Administration should address the mislabeling of the iodine content of prenatal/lactation supplements.

Association between maternal serum perfluoroalkyl substances during pregnancy and maternal and cord thyroid hormones: Taiwan maternal and infant cohort study.

BACKGROUND: Perfluoroalkyl substances (PFASs) are synthetic compounds that are widely used in industry and are often detectable in humans. In pregnant rats and their pups, PFASs can interfere with thyroid hormone homeostasis. In humans, maternal thyroid hormones supply the fetus throughout pregnancy, and thyroid hormones play a critical role in fetal growth and neurodevelopment. OBJECTIVES: We investigated the association between maternal PFAS exposure and thyroid hormone status in pregnant women and neonates. METHODS: In a study of environmental exposure and health in Taiwan, we measured serum concentrations of nine PFASs and four thyroid hormones for 285 pregnant women in their third trimester, and also measured cord serum thyroid hormones for 116 neonates. Associations between maternal PFASs and maternal and cord thyroid hormones were examined in multiple linear regression models. RESULTS: Perfluorohexanesulfonic acid concentrations were positively associated with maternal thyroid-stimulating hormone (TSH) levels. Pregnant women with higher levels of perfluorononanoic acid (PFNA), perfluoroundecanoic acid (PFUnDA), and perfluorododecanoic acid (PFDoDA) had lower free thyroxine (T4) and total T4 levels. For example, we estimated that maternal free T4 levels decreased 0.019 ng/dL (95% CI: -0.028, -0.009) with each nanogram per milliliter increase in maternal PFNA. Finally, maternal PFNA, PFUnDA, and PFDoDA levels were associated with lower cord total triiodothyronine (T3) and total T4 levels, and maternal perfluorodecanoic acid (PFDeA) was associated with lower cord total T3. CONCLUSIONS: Our results suggest that exposure to some PFASs during pregnancy may interfere with thyroid hormone homeostasis in pregnant women and fetuses.

Postnatal exposure to methyl mercury and neuropsychological development in 7-year-old urban inner-city children exposed to lead in the United States.

BACKGROUND: The most common route for general population exposure to methyl mercury (MeHg) is fish consumption. Recommendations to pregnant women about consuming fish contaminated with MeHg are also applied to children, but there are few studies available about the effects of low-level postnatal MeHg exposure in them. OBJECTIVES: To investigate the association between postnatal methyl mercury exposure and neuropsychological development in a study of children also exposed to lead, both measured at 7 years. METHODS: We measured MeHg concentrations in blood samples from the Treatment of Lead-Exposed Children (TLC) trial in which 780 children with elevated concentrations of lead in blood were followed with neuropsychological tests from ages 12-33 months through 7 years. Here we examine blood MeHg concentration and neuropsychological test scores, both measured at age 7 years. We used a maximum likelihood method to estimate geometric mean MeHg concentration and generalized linear regression models to analyze MeHg and neuropsychological test scores. RESULTS: Geometric mean MeHg concentration was 0.56 (95% confidence interval: 0.52, 0.59) µ g/L. A 1  µ g/L increase in MeHg was associated with a 2.1 (95% confidence interval: 0.4, 3.8) point increase in Full-Scale IQ and 0.2 (95% confidence interval: 0.02, 0.4) point increase in Learning Slopeindex T-score on a test of verbal memory. CONCLUSIONS: Our results suggest that the relatively low MeHg exposure in US school-aged children from this population has no detectable adverse effect on neuropsychological development. The positive associations observed between MeHg and neurodevelopment may indirectly reflect consumption of beneficial polyunsaturated fatty acids from seafood.

Urogenital epithelial cells as simple markers of estrogen response in infants: methods and applications.

Exposure to estrogen-mimicking chemicals during critical periods of development, such as infancy, may have adverse effects. However, these effects can be difficult to characterize in most epidemiologic studies. For example, growth of reproductive organs may be susceptible to estrogenic chemicals, but measuring it requires skilled ultrasound examination; timing of pubertal onset may be altered, but observing it requires long-term follow up. To address the need for a simple marker of response to estrogenic exposures in infants, we propose a novel application of a classic marker of estrogen response in adult women: cytological evaluation of urogenital epithelial cells. In this cross-sectional study of 34 female and 41 male infants, we demonstrate that epithelial cells can be obtained from swabs of the vaginal introitus (females) and urethral meatus (males), as well as from spun urine, and that these cells respond to differential estrogenic conditions, as indicated by the relative abundance of the superficial epithelial cell type. To model varying estrogen exposure, we sampled from infants who were either newborn (highly exposed to maternal estrogens), or 12 weeks old (12 W) (negligibly exposed to estrogen). Newborns had a higher percentage of superficial cells (%S), as compared to 12 W (mean ± standard error: 8.3 ± 1.8 vs. 0.9 ± 0.2) (p < 0.01), consistent with an estrogen response. This difference in %S from newborn to 12 W was observed similarly for swab (-7.6 ± 1.7) and urine (-7.3 ± 2.6) specimens and for males (-9.6 ± 2.9) and females (-5.2 ± 2.1). Examination of urogenital epithelial cells can successfully demonstrate estrogen response in both sexes, using cell specimens collected from either swab or urine sampling. In future studies, this simple, non-invasive method may be applied to assess whether estrogen-mimicking chemicals produce an estrogenic response in infants.

Association between perfluoroalkyl substances and thyroid stimulating hormone among pregnant women: a cross-sectional study.

BACKGROUND: Perfluoroalkyl substances (PFASs) are a group of highly persistent chemicals that are widespread contaminants in wildlife and humans. Exposure to PFAS affects thyroid homeostasis in experimental animals and possibly in humans. The objective of this study was to examine the association between plasma concentrations of PFASs and thyroid stimulating hormone (TSH) among pregnant women. METHODS: A total of 903 pregnant women who enrolled in the Norwegian Mother and Child Cohort Study from 2003 to 2004 were studied. Concentrations of thirteen PFASs and TSH were measured in plasma samples collected around the 18th week of gestation. Linear regression models were used to evaluate associations between PFASs and TSH. RESULTS: Among the thirteen PFASs, seven were detected in more than 60% of samples and perfluorooctane sulfonate (PFOS) had the highest concentrations (median, 12.8 ng/mL; inter-quartile range [IQR], 10.1 -16.5 ng/mL). The median TSH concentration was 3.5 (IQR, 2.4 - 4.8) µIU/mL. Pregnant women with higher PFOS had higher TSH levels. After adjustment, with each 1 ng/mL increase in PFOS concentration, there was a 0.8% (95% confidence interval: 0.1%, 1.6%) rise in TSH. The odds ratio of having an abnormally high TSH, however, was not increased, and other PFASs were unrelated to TSH. CONCLUSIONS: Our results suggest an association between PFOS and TSH in pregnant women that is small and may be of no clinical significance.

The impact of succimer chelation on blood cadmium in children with background exposures: a randomized trial.

Succimer lowers blood lead concentrations in children, and the structure of succimer chelates of lead and cadmium are similar. Using blood samples from a randomized trial of succimer for lead poisoning, however, we found that succimer did not lower blood cadmium in children with background exposure.