Emily R. Baker

Rice consumption contributes to arsenic exposure in US women

Emerging data indicate that rice consumption may lead to potentially harmful arsenic exposure. However, few human data are available, and virtually none exist for vulnerable periods such as pregnancy. Here we document a positive association between rice consumption and urinary arsenic excretion, a biomarker of recent arsenic exposure, in 229 pregnant women. At a 6-mo prenatal visit, we collected a urine sample and 3-d dietary record for water, fish/seafood, and rice. We also tested womens home tap water for arsenic, which we combined with tap water consumption to estimate arsenic exposure through water. Women who reported rice intake (n = 73) consumed a median of 28.3 g/d, which is ∼0.5 cup of cooked rice each day. In general linear models adjusted for age and urinary dilution, both rice consumption (g, dry mass/d) and arsenic exposure through water (μg/d) were significantly associated with natural log-transformed total urinary arsenic (, , both P < 0.0001), as well as inorganic arsenic, monomethylarsonic acid, and dimethylarsinic acid (each P < 0.005). Based on total arsenic, consumption of 0.56 cup/d of cooked rice was comparable to drinking 1 L/d of 10 μg As/L water, the current US maximum contaminant limit. US rice consumption varies, averaging ∼0.5 cup/d, with Asian Americans consuming an average of >2 cups/d. Rice arsenic content and speciation also vary, with some strains predominated by dimethylarsinic acid, particularly those grown in the United States. Our findings along with others indicate that rice consumption should be considered when designing arsenic reduction strategies in the United States.

Relation between in Utero Arsenic Exposure and Birth Outcomes in a Cohort of Mothers and Their Newborns from New Hampshire.

Background: Studies suggest that arsenic exposure influences birth outcomes; however, findings are mixed. Objective: We assessed in utero arsenic exposure in relation to birth outcomes and whether maternal prepregnancy weight and infant sex modified the associations. Methods: Among 706 mother–infant pairs exposed to low levels of arsenic through drinking water and diet, we assessed in utero arsenic exposure using maternal second-trimester urinary arsenic, maternal prepregnancy weight through self-report, and birth outcomes from medical records. Results: Median (interquartile range) of total urinary arsenic [tAs; inorganic arsenic (iAs) + monomethylarsonic acid (MMA) + dimethylarsinic acid (DMA)] was 3.4 μg/L (1.7–6.0). In adjusted linear models, each doubling of tAs was associated with a 0.10-cm decrease (95% CI: –0.19, –0.01) in head circumference. Results were similar for MMA and DMA. Ln(tAs) and ln(DMA) were positively associated with birth length in infant males only; among males, each doubling of tAs was associated with a 0.28-cm increase (95% CI: 0.09, 0.46) in birth length (pinteraction = 0.04). Results were similar for DMA. Additionally, arsenic exposure was inversely related to ponderal index, and associations differed by maternal weight. Each ln(tAs) doubling of tAs was associated with a 0.55-kg/m3 lower (95% CI: –0.82, –0.28, p < 0.001) ponderal index for infants of overweight/obese, but not normal-weight, mothers (pinteraction < 0.01). Finally, there was a significant interaction between maternal weight status, infant sex, and arsenic exposure on birth weight (pinteraction = 0.03). In girls born of overweight/obese mothers, each doubling of tAs was associated with a 62.9-g decrease (95% CI: –111.6, –14.2) in birth weight, though the association was null in the other strata. Conclusions: Low-level arsenic exposure may affect fetal growth, and the associations may be modified by maternal weight status and infant sex. Citation: Gilbert-Diamond D, Emond JA, Baker ER, Korrick SA, Karagas MR. 2016. Relation between in utero arsenic exposure and birth outcomes in a cohort of mothers and their newborns from New Hampshire. Environ Health Perspect 124:1299–1307; http://dx.doi.org/10.1289/ehp.1510065

Infant Infections and Respiratory Symptoms in Relation to in Utero Arsenic Exposure in a U.S. Cohort.

Background: Arsenic has been linked to disrupted immune function and greater infection susceptibility in highly exposed populations. Well arsenic levels above the U.S. EPA limit occur in our U.S. study area and are of particular concern for pregnant women and infants. Objectives: We investigated whether in utero arsenic exposure affects the risk of infections and respiratory symptoms over the first year of life. Methods: We prospectively obtained information on infant infections and symptoms, including their duration and treatment (n = 412) at 4, 8, and 12 months using a parental telephone survey. Using generalized estimating equation models adjusted for potential confounders, we evaluated the association between maternal pregnancy urinary arsenic and infant infections and symptoms over the first year. Results: Each doubling of maternal urinary arsenic was related to increases in the total number of infections requiring prescription medication in the first year [relative risk (RR) = 1.1; 95% CI: 1.0, 1.2]. Urinary arsenic was related specifically to respiratory symptoms (difficulty breathing, wheezing, and cough) lasting ≥ 2 days or requiring prescription medication (RR = 1.1; 95% CI: 1.0, 1.2; and RR = 1.2; 95% CI: 1.0, 1.5, respectively), and wheezing lasting ≥ 2 days, resulting in a doctor visit or prescription medication treatment (RR = 1.3; 95% CI: 1.0, 1.7; RR = 1.3; 95% CI: 1.0, 1.8, and RR = 1.5; 95% CI: 1.0, 2.2, respectively). Associations also were observed with diarrhea (RR = 1.4; 95% CI: 1.1, 1.9) and fever resulting in a doctor visit (RR = 1.2; 95% CI: 1.0, 1.5). Conclusions: In utero arsenic exposure was associated with a higher risk of infection during the first year of life in our study population, particularly infections requiring medical treatment, and with diarrhea and respiratory symptoms. Citation: Farzan SF, Li Z, Korrick SA, Spiegelman D, Enelow R, Nadeau K, Baker E, Karagas MR. 2016. Infant infections and respiratory symptoms in relation to in utero arsenic exposure in a U.S. cohort. Environ Health Perspect 124:840–847; http://dx.doi.org/10.1289/ehp.1409282

Infant toenails as a biomarker of in utero arsenic exposure

A growing body of evidence suggests that in utero and early-life exposure to arsenic may have detrimental effects on children, even at the low to moderate levels common in the United States and elsewhere. In a sample of 170 mother–infant pairs from New Hampshire, we determined infant exposure to in utero arsenic by evaluating infant toenails as a biomarker using inductively coupled plasma mass spectrometry. Infant toenail arsenic concentration correlated with maternal postpartum toenail concentrations (Spearman’s correlation coefficient 0.34). In adjusted linear models, a doubling of maternal toenail arsenic concentration was associated with a 53.8% increase in infant toenail arsenic concentration as compared with 20.4% for a doubling of maternal urine arsenic concentration. In a structural equation model, a doubling of the latent variable integrating maternal toenail and urine arsenic concentrations was associated with a 67.5% increase in infant toenail arsenic concentration. A similar correlation between infant and maternal postpartum toenail concentrations was observed in a validation cohort of 130 mother–infant pairs from Rhode Island. In utero exposure to arsenic occurs through maternal water and dietary sources, and infant toenails appear to be a reliable biomarker for estimating arsenic exposure during the critical window of gestation.

Placental arsenic concentrations in relation to both maternal and infant biomarkers of exposure in a US cohort

Arsenic crosses the placenta and may have adverse consequences in utero and later in life. At present, little is known about arsenic concentrations in placenta and their relation to maternal and infant exposures particularly at common levels of exposure. We measured placenta arsenic in a US cohort potentially exposed via drinking water from private wells, and evaluated the relationships between placenta and maternal and infant biomarker arsenic concentrations. We measured total arsenic concentrations in placental samples from women enrolled in the New Hampshire Birth Cohort Study (N=766). We compared these data to maternal urinary arsenic (total arsenic and individual species) collected at approximately 24-28 week gestation, along with maternal post-partum toenails and infant toenails using non-parametric multivariate analysis of log10-transformed data. We also examined the association between placental arsenic and household drinking water arsenic. Placenta arsenic concentrations were related to arsenic concentrations in maternal urine (β 0.55, P value <0.0001), maternal (β 0.30, P value 0.0196) and infant toenails (β 0.40, P value 0.0293) and household drinking water (β 0.09, P value <0.0001). Thus, our data suggest that placenta arsenic concentrations reflect both maternal and infant exposures.

Placental Metal Concentrations in Relation to Maternal and Infant Toenails in a U.S. Cohort

Metal contaminants cross the placenta, presenting a heightened risk of perturbing fetal development. Information about placental concentrations and transfer of multiple potentially toxic metals from low to moderate exposure is lacking. We measured concentrations of Cd, Pb, Hg, Mn, Se, and Zn in 750 placentas collected from women enrolled in the New Hampshire Birth Cohort Study and examined the correlation between elements, and profiles of potentially toxic metals (Cd, Pb, Hg, and Mn) stratified by nutrient concentrations (Zn and Se) using principal components analyses. We further examined the indirect effects of maternal metal concentrations on infant metal concentrations through placental metal concentrations using structural equation models. Placental metal concentrations were all correlated, particularly Zn and Mn, and Zn and Cd, and the principal component of metals differed by stratum of high versus low Zn and Se. Associations were observed between placenta and maternal toenail Se (β = 63.49; P < 0.0001) and Pb (β = 0.90; P < 0.0001) but not other metals. Structural equation models did not indicate any statistically significant indirect effects through placental metal concentrations. Placental metal concentrations may represent a distinct biomarker of metal exposure and adverse health impacts to the fetus, particularly those stemming from the placenta.

Blood Pressure Changes in Relation to Arsenic Exposure in a U.S. Pregnancy Cohort

Background Inorganic arsenic exposure has been related to the risk of increased blood pressure based largely on cross-sectional studies conducted in highly exposed populations. Pregnancy is a period of particular vulnerability to environmental insults. However, little is known about the cardiovascular impacts of arsenic exposure during pregnancy. Objectives We evaluated the association between prenatal arsenic exposure and maternal blood pressure over the course of pregnancy in a U.S. population. Methods The New Hampshire Birth Cohort Study is an ongoing prospective cohort study in which > 10% of participant household wells exceed the arsenic maximum contaminant level of 10 μg/L established by the U.S. EPA. Total urinary arsenic measured at 24–28 weeks gestation was measured and used as a biomarker of exposure during pregnancy in 514 pregnant women, 18–45 years of age, who used a private well in their household. Outcomes were repeated blood pressure measurements (systolic, diastolic, and pulse pressure) recorded during pregnancy. Results Using linear mixed effects models, we estimated that, on average, each 5-μg/L increase in urinary arsenic was associated with a 0.15-mmHg (95% CI: 0.02, 0.29; p = 0.022) increase in systolic blood pressure per month and a 0.14-mmHg (95% CI: 0.02, 0.25; p = 0.021) increase in pulse pressure per month over the course of pregnancy. Conclusions In our U.S. cohort of pregnant women, arsenic exposure was associated with greater increases in blood pressure over the course of pregnancy. These findings may have important implications because even modest increases in blood pressure impact cardiovascular disease risk. Citation Farzan SF, Chen Y, Wu F, Jiang J, Liu M, Baker E, Korrick SA, Karagas MR. 2015. Blood pressure changes in relation to arsenic exposure in a U.S. pregnancy cohort. Environ Health Perspect 123:999–1006; http://dx.doi.org/10.1289/ehp.1408472

The New Hampshire Perinatal Program: twenty years of perinatal outreach education.

OBJECTIVE:To describe 20 years of regional outreach education by the New Hampshire Perinatal Program, its interaction with all 26 community hospitals in the state with maternity services and an additional four in adjoining Vermont.STUDY DESIGN:This paper describes educational initiatives responsive to the needs of perinatal physicians and nurses. The core of the program is the transport conference held annually at each referring hospital in which maternal–fetal and infant referrals are discussed. There are additional community hospital-based programs, programs at convenient locations in the region and medical center conferences and skills programs.RESULTS:The program annually awards 10,000 continuing medical education credits (CME) and nursing contact hours. Evaluation and feedback from all participants is encouraged. New Hampshire has one of the lowest perinatal mortality rates in the county, which reflects in part the accomplishments of the program.CONCLUSION:Perinatal outreach education is a shared responsibility of providers in both the academic center and community hospitals and is necessary to ensure optimal care for mothers and infants.

Better Diet Quality during Pregnancy Is Associated with a Reduced Likelihood of an Infant Born Small for Gestational Age: An Analysis of the Prospective New Hampshire Birth Cohort Study

Background Birth weight has a U-shaped relation with chronic disease. Diet quality during pregnancy may impact fetal growth and infant birth weight, yet findings are inconclusive. Objective We examined the relation between maternal diet quality during pregnancy and infant birth size among women enrolled in a prospective birth cohort. Methods Women 18-45 y old with a singleton pregnancy were recruited at 24-28 wk of gestation from prenatal clinics in New Hampshire. Women completed a validated food frequency questionnaire at enrollment. Diet quality was computed as adherence to the Alternative Healthy Eating Index. Infant birth outcomes (sex, head circumference, weight, and length) were extracted from medical records. Weight-for-length z scores, low birth weight, macrosomia, and size for gestational age [small for gestational age (SGA) or large for gestational age (LGA)] were computed. Multivariable regression models fit each outcome on quartiles of diet quality, adjusted for covariates. Models were computed overall and stratified by smoking status. Results Analyses included 862 women and infants with complete data. Lower diet quality was associated with lower maternal education, being a smoker, prepregnancy obesity status, and lack of exercise during pregnancy. Overall, 3.4% of infants were born with a low birth weight, 12.1% with macrosomia, 4.6% were SGA, and 8.7% were LGA. In an adjusted model, increased diet quality appeared linearly associated with a reduced likelihood of SGA (P-trend = 0.03), although each quartile comparison did not reach statistical significance. Specifically, ORs for SGA were 0.89 (95% CI: 0.37, 2.15), 0.73 (95% CI: 0.28, 1.89), and 0.35 (95% CI: 0.11, 1.08) for each increasing quartile of diet quality compared to the lowest quartile. Similar trends for SGA were observed among non-smokers (n = 756; P-trend = 0.07). Also among non-smokers, increased diet quality was associated with lower infant birth weight (P-trend = 0.03) and a suggested reduction in macrosomia (P-trend = 0.07). Conclusions Increased diet quality during pregnancy was related to a reduced risk of SGA in this cohort of pregnant women from New Hampshire. Additional studies are needed to elucidate the relation between maternal diet quality and macrosomia.

Fetal-sex dependent genomic responses in the circulating lymphocytes of arsenic-exposed pregnant women in New Hampshire

Exposure to inorganic arsenic (iAs) during pregnancy is associated with adverse health outcomes present both at birth and later in life. A biological mechanism may include epigenetic and genomic alterations in fetal genes involved in immune functioning. To investigate the role of the maternal immune response to in utero iAs exposure, we conducted an analysis of the expression of immune-related genes in pregnant women from the New Hampshire Birth Cohort Study. A set of 31 genes was identified with altered expression in association with levels of urinary total arsenic, urinary iAs, urinary monomethylated arsenic and urinary dimethylated arsenic. Notably, maternal gene expression signatures differed when stratified on fetal sex, with a more robust inflammatory response observed in male pregnancies. Moreover, the differentially expressed genes were also related to birth outcomes. These findings highlight the sex-dependent nature of the maternal iAs-induced inflammatory response in relationship to fetal outcomes.