Ana M. Mora

Blood and hair manganese concentrations in pregnant women from the infants' environmental health study (ISA) in Costa Rica.

Manganese (Mn), an essential nutrient, is a neurotoxicant at high concentrations. We measured Mn concentrations in repeated blood and hair samples collected from 449 pregnant women living near banana plantations with extensive aerial spraying of Mn-containing fungicide mancozeb in Costa Rica, and examined environmental and lifestyle factors associated with these biomarkers. Mean blood Mn and geometric mean hair Mn concentrations were 24.4 μg/L (8.9–56.3) and 1.8 μg/g (0.05–53.3), respectively. Blood Mn concentrations were positively associated with gestational age at sampling (β = 0.2; 95% CI: 0.1 to 0.2), number of household members (β = 0.4; 95% CI: 0.1 to 0.6), and living in a house made of permeable and difficult-to-clean materials (β = 2.6; 95% CI: 1.3 to 4.0); and inversely related to smoking (β = −3.1; 95% CI: −5.8 to −0.3). Hair Mn concentrations were inversely associated with gestational age at sampling (% change = 0.8; 95% CI: −1.6 to 0.0); and positively associated with living within 50 m of a plantation (% change = 42.1; 95% CI: 14.2 to 76.9) and Mn concentrations in drinking water (% change = 17.5; 95% CI: 12.2 to 22.8). Our findings suggest that pregnant women living near banana plantations aerially sprayed with mancozeb may be environmentally exposed to Mn.

Sociodemographic and Perinatal Predictors of Early Pregnancy Per- and Polyfluoroalkyl Substance (PFAS) Concentrations

Per- and polyfluoroalkyl substances (PFASs), used in food packaging and stain-resistant coatings, are suspected developmental toxicants that are ubiquitous and persistent in the environment. We measured plasma PFAS concentrations during early pregnancy (median = 9.7 weeks gestation) among 1645 women in the Boston-area Project Viva cohort, recruited during 1999-2002. We used multivariable linear regression to estimate associations of sociodemographic and perinatal predictors, including measures of pregnancy physiology (albumin, glomerular filtration rate (GFR)), with log-transformed plasma PFAS concentrations. Geometric mean concentrations for the four main PFASs, perfluorooctanesulfonate (PFOS), perfluorooctanoate (PFOA), perfluorohexanesulfonate (PFHxS) and perfluorononanoate (PFNA) were 25.4, 5.7, 2.5, and 0.6 ng/mL, respectively, comparable with general U.S. population concentrations during those years. Higher early pregnancy PFAS concentrations were associated with younger age (except PFNA), less educational attainment, nulliparity, no history of breastfeeding and higher prepregnancy body mass index in adjusted models. In addition, lower GFR was associated with 3-4% higher PFAS concentrations and higher albumin was associated with 4-6% higher PFAS concentrations. Our results show associations consistent (parity and breastfeeding) and less consistent (age and education) with previous studies. We also report associations with GFR and albumin, which were strongly related to PFAS concentrations and thus could confound estimates of PFAS-outcome associations in epidemiologic studies.

Prenatal and postnatal manganese teeth levels and neurodevelopment at 7, 9, and 10.5 years in the CHAMACOS cohort

BACKGROUND Numerous cross-sectional studies of school-age children have observed that exposure to manganese (Mn) adversely affects neurodevelopment. However, few prospective studies have looked at the effects of both prenatal and postnatal Mn exposure on child neurodevelopment. METHODS We measured Mn levels in prenatal and early postnatal dentine of shed teeth and examined their association with behavior, cognition, memory, and motor functioning in 248 children aged 7, 9, and/or 10.5 years living near agricultural fields treated with Mn-containing fungicides in California. We used generalized linear models and generalized additive models to test for linear and nonlinear associations, and generalized estimating equation models to assess longitudinal effects. RESULTS We observed that higher prenatal and early postnatal Mn levels in dentine of deciduous teeth were adversely associated with behavioral outcomes, namely internalizing, externalizing, and hyperactivity problems, in boys and girls at 7 and 10.5 years. In contrast, higher Mn levels in prenatal and postnatal dentine were associated with better memory abilities at ages 9 and 10.5, and better cognitive and motor outcomes at ages 7 and 10.5 years, among boys only. Higher prenatal dentine Mn levels were also associated with poorer visuospatial memory outcomes at 9 years and worse cognitive scores at 7 and 10.5 years in children with higher prenatal lead levels (≥0.8 μg/dL). All these associations were linear and were consistent with findings from longitudinal analyses. CONCLUSIONS We observed that higher prenatal and early postnatal Mn levels measured in dentine of deciduous teeth, a novel biomarker that provides reliable information on the developmental timing of exposures to Mn, were associated with poorer behavioral outcomes in school-age boys and girls and better motor function, memory, and/or cognitive abilities in school-age boys. Additional research is needed to understand the inconsistencies in the neurodevelopmental findings across studies and the degree to which differences may be associated with different Mn exposure pathways and biomarkers.

Prenatal Exposure to Perfluoroalkyl Substances and Adiposity in Early and Mid-Childhood.

Background: Few studies have examined whether prenatal exposure to perfluoroalkyl substances (PFASs) is associated with childhood adiposity. Objective: We examined associations of prenatal exposure to PFASs with adiposity in early and mid-childhood. Methods: We measured plasma PFAS concentrations in 1,645 pregnant women (median, 9.6 weeks gestation) enrolled in Project Viva, a prospective pre-birth cohort study in Massachusetts (USA), between 1999 and 2002. We assessed overall and central adiposity in 1,006 children in early childhood (median, 3.2 years) and 876 in mid-childhood (median, 7.7 years) using anthropometric and dual X-ray absorptiometry (DXA) measurements. We fitted multivariable linear regression models to estimate exposure-outcome associations and evaluated effect modification by child sex. Results: Median (25–75th percentiles) prenatal plasma perfluorooctanoate (PFOA), perfluorooctane sulfonate (PFOS), perfluorohexane sulfonate (PFHxS), and perfluorononanoate (PFNA) concentrations in children assessed in early childhood were 5.6 (4.1–7.7), 24.8 (18.4–33.9), 2.4 (1.6–3.8), and 0.6 (0.5–0.9) ng/mL, respectively. Among girls, each interquartile range increment of prenatal PFOA concentrations was associated with 0.21 kg/m2 (95% CI: –0.05, 0.48) higher body mass index, 0.76 mm (95% CI: –0.17, 1.70) higher sum of subscapular and triceps skinfold thickness, and 0.17 kg/m2 (95% CI: –0.02, 0.36) higher DXA total fat mass index in mid-childhood. Similar associations were observed for PFOS, PFHxS, and PFNA. We observed null associations for boys and early-childhood adiposity measures. Conclusions: In this cohort, prenatal exposure to PFASs was associated with small increases in adiposity measurements in mid-childhood, but only among girls. Citation: Mora AM, Oken E, Rifas-Shiman SL, Webster TF, Gillman MW, Calafat AM, Ye X, Sagiv SK. 2017. Prenatal exposure to perfluoroalkyl substances and adiposity in early and mid-childhood. Environ Health Perspect 125:467–473; http://dx.doi.org/10.1289/EHP246

Manganese in teeth and neurodevelopment in young Mexican-American children.

INTRODUCTION Manganese (Mn) is an essential nutrient but higher exposure has been associated with poorer neurodevelopment in children. METHODS We measured Mn levels in prenatal (Mnpre) (n=197) and postnatal (Mnpost) dentin (n=193) from childrens shed teeth using laser ablation inductively coupled plasma mass spectroscopy and examined the relationship with childrens scores on the Mental Development Index (MDI) and Psychomotor Development Index (PDI) on the Bayley Scales of Infant Development at 6, 12, and 24-months. We explored non-linear associations and interactions by sex, blood lead concentrations and maternal iron status during pregnancy. RESULTS A two-fold increase of Mnpost levels in dentin was associated with small decreases in MDI at 6-months and 12-months of age. We also observed a non-linear relationship between Mnpost levels and PDI at 6-months. We found effect modification by sex for Mnpost levels and neurodevelopment at 6-months with stronger effects among girls for both MDI (-1.5 points; 95% Confidence Interval (CI): -2.4, -0.6) and PDI (-1.8 points; 95% CI: -3.3, -0.3). Girls whose mothers had lower hemoglobin levels experienced larger decreases in MDI and PDI associated with Mnpre levels than girls whose mothers had higher hemoglobin levels (pinteraction=0.007 and 0.09, respectively). We did not observe interactions with blood lead concentrations or any relationships with neurodevelopment at 24-months. CONCLUSIONS Using Mn measurements in tooth dentin, a novel biomarker that provides prenatal and early postnatal levels, we observed negative transient associations between postnatal Mn levels and early neurodevelopment with effect modification by sex and interactions with prenatal hemoglobin.

Prenatal DDT and DDE exposure and child IQ in the CHAMACOS cohort.

Although banned in most countries, dichlorodiphenyl-trichloroethane (DDT) continues to be used for vector control in some malaria endemic areas. Previous findings from the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) cohort study found increased prenatal levels of DDT and its breakdown product dichlorodiphenyl-dichloroethylene (DDE) to be associated with altered neurodevelopment in children at 1 and 2years of age. In this study, we combined the measured maternal DDT/E concentrations during pregnancy obtained for the prospective birth cohort with predicted prenatal DDT and DDE levels estimated for a retrospective birth cohort. Using generalized estimating equation (GEE) and linear regression models, we evaluated the relationship of prenatal maternal DDT and DDE serum concentrations with childrens cognition at ages 7 and 10.5years as assessed using the Full Scale Intelligence Quotient (IQ) and 4 subtest scores (Working Memory, Perceptual Reasoning, Verbal Comprehension, and Processing Speed) of the Wechsler Intelligence Scale for Children (WISC). In GEE analyses incorporating both age 7 and 10.5 scores (n=619), we found prenatal DDT and DDE levels were not associated with Full Scale IQ or any of the WISC subscales (p-value>0.05). In linear regression analyses assessing each time point separately, prenatal DDT levels were inversely associated with Processing Speed at age 7years (n=316), but prenatal DDT and DDE levels were not associated with Full Scale IQ or any of the WISC subscales at age 10.5years (n=595). We found evidence for effect modification by sex. In girls, but not boys, prenatal DDE levels were inversely associated with Full Scale IQ and Processing Speed at age 7years. We conclude that prenatal DDT levels may be associated with delayed Processing Speed in children at age 7years and the relationship between prenatal DDE levels and childrens cognitive development may be modified by sex, with girls being more adversely affected.

Biomarkers of manganese exposure in pregnant women and children living in an agricultural community in California.

Manganese (Mn) is an essential nutrient but at high exposure levels is a neurotoxicant. There is no well-validated biomarker to assess perinatal Mn exposure. A total of 75 mother-child pairs provided blood, urine, and/or deciduous tooth samples. We analyzed Mn in dentin and enamel of shed teeth; maternal, cord, and child blood; and maternal and child urine and examined the interrelationships of Mn levels in all matrices. We observed higher Mn levels in prenatal than postnatal dentin (geometric mean (GM) = 0.51 vs 0.16 Mn:Ca, p < 0.001), maternal blood at delivery than 26 weeks gestation (GM = 20.7 vs. 14.6 μg/L, p = 0.001), and cord blood than child blood at 24 months of age (39.9 vs 25.0 μg/L, p = 0.005). There were no significant correlations between Mn in dentin and Mn concentrations in maternal blood or maternal or child urine. Levels of Mn in prenatal dentin, prenatal maternal blood, and 24 month urine were higher (p < 0.05) among mothers and children living with a farm worker. Prenatal Mn levels in dentin were correlated with Mn loadings and concentrations in prenatal house dust. Levels of Mn measured in tooth dentin constitute a promising biomarker of perinatal exposure.

Aerial application of mancozeb and urinary ethylene thiourea (ETU) concentrations among pregnant women in Costa Rica: the Infants' Environmental Health Study (ISA).

Background: Mancozeb and its main metabolite ethylene thiourea (ETU) may alter thyroid function; thyroid hormones are essential for fetal brain development. In Costa Rica, mancozeb is aerially sprayed at large-scale banana plantations on a weekly basis. Objectives: Our goals were to evaluate urinary ETU concentrations in pregnant women living near large-scale banana plantations, compare their estimated daily intake (EDI) with established reference doses (RfDs), and identify factors that predict their urinary ETU concentrations. Methods: We enrolled 451 pregnant women from Matina County, Costa Rica, which has large-scale banana production. We visited 445 women up to three times during pregnancy to obtain urine samples (n = 872) and information on factors that possibly influence exposure. We determined urinary ETU concentrations using liquid chromatography mass spectrometry. Results: Pregnant women’s median urinary ETU concentrations were more than five times higher than those reported for other general populations. Seventy-two percent of the women had EDIs above the RfD. Women who lived closest (1st quartile, < 48 m) to banana plantations on average had a 45% (95% CI: 23, 72%) higher urinary ETU compared with women who lived farthest away (4th quartile, ≥ 565 m). Compared with the other women, ETU was also higher in women who washed agricultural work clothes on the day before sampling (11%; 95% CI: 4.9, 17%), women who worked in agriculture during pregnancy (19%; 95% CI: 9.3, 29%), and immigrant women (6.2%; 95% CI: 1.0, 13%). Conclusions: The pregnant women’s urinary ETU concentrations are of concern, and the principal source of exposure is likely to be aerial spraying of mancozeb. The factors predicting ETU provide insight into possibilities for exposure reduction. Citation: van Wendel de Joode B, Mora AM, Córdoba L, Cano JC, Quesada R, Faniband M, Wesseling C, Ruepert C, Öberg M, Eskenazi B, Mergler D, Lindh CH. 2014. Aerial application of mancozeb and urinary ethylene thiourea (ETU) concentrations among pregnant women in Costa Rica: The Infants’ Environmental Health Study (ISA). Environ Health Perspect 122:1321–1328; http://dx.doi.org/10.1289/ehp.1307679

Early-Life Exposure to Perfluoroalkyl Substances and Childhood Metabolic Function

Background: Perfluoroalkyl substances (PFASs) are synthetic chemicals that may persist in the environment and in humans. There is a possible association between early-life PFAS exposure and metabolic dysfunction in later life, but data are limited. Methods: We studied 665 mother–child pairs in Project Viva, a Boston, Massachusetts-area cohort recruited 1999–2002. We quantified concentrations of PFASs [perfluorooctanoate (PFOA), perfluorooctane sulfonate (PFOS), perfluorononanoate (PFNA), perfluorohexane sulfonate (PFHxS), and perfluorodecanoate (PFDeA)] in maternal plasma collected at the first prenatal visit (median, 9.6 weeks gestation) and in child plasma from the mid-childhood research visit (median, 7.7 years). We assessed leptin, adiponectin, and homeostatic model assessment of insulin resistance (HOMA-IR) in mid-childhood. We fit covariate-adjusted linear regression models and conducted stratified analyses by child sex. Results: Children with higher PFAS concentrations had lower HOMA-IR [e.g., –10.1% (95% CI: –17.3, –2.3) per interquartile range increment in PFOA]. This inverse association between child PFAS and HOMA-IR was more pronounced in females [e.g., PFOA: –15.6% (95% CI: –25.4, –4.6) vs. –6.1% (95% CI: –16.2, 5.2) for males]. Child PFAS plasma concentrations were not associated with leptin or adiponectin. Prenatal PFAS plasma concentrations were not associated with leptin, adiponectin, or HOMA-IR in offspring. Conclusions: We found no evidence for an adverse effect of early-life PFAS exposure on metabolic function in mid-childhood. In fact, children with higher PFAS concentrations had lower insulin resistance. Citation: Fleisch AF, Rifas-Shiman SL, Mora AM, Calafat AM, Ye X, Luttmann-Gibson H, Gillman MW, Oken E, Sagiv SK. 2017. Early-life exposure to perfluoroalkyl substances and childhood metabolic function. Environ Health Perspect 125:481–487; http://dx.doi.org/10.1289/EHP303

Indigenous children living nearby plantations with chlorpyrifos-treated bags have elevated 3,5,6-trichloro-2-pyridinol (TCPy) urinary concentrations

BACKGROUND The US Environmental Protection Agency voluntary phased-out residential use of chlorpyrifos in 2001. In contrast, in Costa Rica, chlorpyrifos-treated bags are increasingly used to protect banana and plantain fruits from insects and to fulfill product standards, even in populated areas. OBJECTIVES To evaluate childrens exposure to chlorpyrifos in villages situated nearby banana plantations and plantain farms in Costa Rica. METHODS The study targeted two villages with use of chlorpyrifos-treated bags in nearby banana plantations and plantain farms and one village with mainly organic production. For 140 children from these villages, mostly indigenous Ngäbe and Bribri, parent-interviews and urine samples (n=207) were obtained. Urinary 3,5,6-trichloro-2-pyridinol (TCPy) levels were measured as a biomarker for chlorpyrifos exposure. In the banana and plantain village also environmental contamination to chlorpyrifos was explored. RESULTS Children from the banana and plantain villages had statistically significant higher urinary TCPy concentrations than children from the referent village; 2.6 and 2.2 versus 1.3μg/g creatinine, respectively. Chlorpyrifos was detected in 30% of the environmental samples as well as in 92% of the hand/foot wash samples. For more than half of the children their estimated intake exceeded the US EPA chronic population adjusted dose. For some, the acute population adjusted dose and the chronic reference dose were also exceeded. CONCLUSIONS Our results suggest that children living nearby plantations with chlorpyrifos-treated bags are exposed to chlorpyrifos levels that may affect their health. Interventions to reduce chlorpyrifos exposure are likely to improve childrens health and environment in banana and plantain growing regions.