Prenatal exposure to arsenic and lung function in children from the New Hampshire Birth Cohort Study.
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SUBMITTER: Signes-Pastor AJ
PROVIDER: S-EPMC8353991 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BACKGROUND:Increasing evidence suggests that prenatal exposure to arsenic, even at common environmental levels, adversely affects child health. These adverse effects include impaired fetal growth, which can carry serious health implications lifelong. However, the mechanisms by which arsenic affects fetal health and development remain unclear. METHODS:We addressed this question using a group of 46 pregnant women selected from the New Hampshire Birth Cohort Study (NHBCS), a US cohort exposed to low-to-moderate arsenic levels in drinking water through the use of unregulated private wells. Prenatal arsenic exposure was assessed using maternal urine samples taken at mid-gestation. Samples of the fetal portion of the placenta were taken from the base of the umbilical cord insertion at the time of delivery, stored in RNAlater and frozen. We used RNA sequencing to analyze changes in global gene expression in the fetal placenta associated with in utero arsenic exposure, adjusting for maternal age. Gene set enrichment analysis and enrichment mapping were then used to identify biological processes represented by the differentially expressed genes. Since our previous analyses have identified considerable sex differences in placental gene expression associated with arsenic exposure, we analyzed male and female samples separately. RESULTS:At FDR?<?0.05, no genes were differentially expressed in female placenta, while 606 genes were differentially expressed in males. Genes showing the most significant associations with arsenic exposure in females were LEMD1 and UPK3B (fold changes 2.51 and 2.48), and in males, FIBIN and RANBP3L (fold changes 0.14 and 0.15). In gene set enrichment analyses, at FDR?<?0.05, a total of 211 gene sets were enriched with differentially expressed genes in female placenta, and 154 in male placenta. In female but not male placenta, 103 of these gene sets were also associated with reduced birth weight. CONCLUSIONS:Our results reveal multiple biological functions in the fetal placenta that are potentially affected by increased arsenic exposure, a subset of which is sex-dependent. Further, our data suggest that in female infants, the mechanisms underlying the arsenic-induced reduction of birth weight may involve activation of stress response pathways.
| S-EPMC6868717 | biostudies-literature
Project description:Infants and young children commonly consume apple-based products, which may contain high concentrations of inorganic arsenic (iAs). As yet, iAs exposure from ingesting apple products has not been well-characterized in early childhood. Therefore, we investigated the association between urinary arsenic concentrations and intake of apple products in one-year-old infants participating in the New Hampshire Birth Cohort Study. A three-day food diary prior to collection of a spot urine sample was used to determine infant's consumption of apple products. The sum of urinary iAs, monomethylarsonic acid, and dimethylarsinic acid, referred to as ΣAs, was used to estimate iAs exposure. A total of 242 infants had urinary arsenic speciation analyzed without indication of fish/seafood consumption (urinary arsenobetaine < 1 μg/L) and with a completed three-day food diary. Of these, 183 (76%) infants ate apples or products containing apple. The geometric mean urinary ΣAs among the 59 infants who did not consume any type of apple product was 2.78 μg/L as compared to 2.38, 2.46, 2.28, and 2.73 μg/L among infants who exclusively consumed apple juice (n = 30), apple puree (n = 67), apples as whole fruit (n = 20) or products mixed with apples (n = 21), respectively. Differences in urinary ΣAs associated with apple consumption were not statistically significant in generalized linear models adjusted for urine dilution, rice consumption, and household water arsenic. Thus, while infants in our study frequently consumed apples and apple products, we did not find evidence that it increased iAs exposure.
| S-EPMC7665059 | biostudies-literature
Project description:BACKGROUND:Mechanistic studies support the potential for mercury (Hg) to alter immunity, including via in utero exposure. As yet, there are few prospective studies of in utero Hg exposure and subsequent immune-related outcomes, especially in infancy. OBJECTIVES:We investigated the association of biomarkers of prenatal Hg exposure and maternal silver-mercury dental amalgams with the occurrence of infant allergy, respiratory infection, and respiratory symptoms in the first year of life. METHODS:The New Hampshire Birth Cohort Study (NHBCS) ascertained information on infant allergies, infections and symptoms through telephone interviews at 4, 8 and 12 months postpartum and measured total Hg in maternal toenails collected at ~28-30 weeks gestation. Information on maternal fish consumption and presence of dental amalgams was obtained from a questionnaire administered at study enrollment at 24-28 weeks. A total of 1321 NHBCS mother-infant pairs had at least one Hg exposure measure (toenail Hg or information on dental amalgams) and information on dietary fish intake. Generalized linear models and generalized estimating equation models with Poisson regression adjusted for potential confounders (maternal age, level of education, parity, smoking, alternative Healthy Eating Index-2010, infant sex, gestational age, feeding mode, and day care attendance) were used to assess the association between infant outcomes and prenatal toenail Hg levels. We subsetted this analysis on mothers who consumed fish (n = 706) as a measure of in utero methylmercury (MeHg) exposure. Associations between infant outcomes and dental amalgams as a measure of in utero inorganic Hg exposure were assessed among mothers who did not consume fish (n = 218). RESULTS:Among women who ate fish during pregnancy, higher maternal toenail Hg concentrations were associated with an increased risk of lower respiratory infections and respiratory symptoms requiring a doctor visit among infants age 9-12 months (relative risk (RR) 1.4 (95% CI: 1.1, 1.9) and 1.2 (95% CI: 1.0, 1.4) respectively), whereas a reduced risk of lower respiratory infections was observed among infants 0-4 months of age (RR = 0.7 (95% CI: 0.5, 1.0). We found little to no evidence of associations of toenail Hg with upper respiratory infections, allergy or eczema at any age to one year. Among infants of mothers who did not consume fish, we found an elevated risk of upper respiratory infections requiring a doctor visit in relation to having dental amalgams during pregnancy (RR = 1.5 (95% CI: 1.1, 2.1)). Overall, weaker associations were observed with lower respiratory infections, respiratory symptoms, and medically confirmed allergies, and there was no association with eczema. CONCLUSIONS:Our analyses of a US birth cohort, along with prior mechanistic work, raise the possibility that gestational Hg exposure through fish/seafood consumption and dental amalgams may alter respiratory infections and respiratory symptoms in infants.
| S-EPMC6561090 | biostudies-literature
Project description:Arsenic is one of the most commonly encountered environmental toxicants, and research from model systems has suggested that one mode of its toxic activity may be through alterations in DNA methylation. In utero exposure to arsenic can affect fetal, newborn, and infant health, resulting in a range of phenotypic outcomes.This study examined variation in placental DNA methylation and its relationship to arsenic exposure in 343 individuals enrolled in the New Hampshire Birth Cohort Study.Linear regression models using a reference-free correction to account for cellular composition were employed to determine CpG loci affected by arsenic levels.Total arsenic measured in maternal urine during the second trimester was not associated with methylation in the placenta, whereas arsenic levels quantified through maternal toenail collected at birth were associated with methylation at a single CpG locus (p = 4.1 × 10-8). Placenta arsenic levels were associated with 163 differentially methylated loci (false discovery rate < 0.05), with 11 probes within the LYRM2 gene reaching genome-wide significance (p < 10-8). Measurement of LYRM2 mRNA levels indicated that methylation was weakly to moderately correlated with expression (r = 0.15, p < 0.06). In addition, we identified pathways suggesting changes in placental cell subpopulation proportions associated with arsenic exposure.These data demonstrate the potential for arsenic, even at levels commonly experienced in a U.S. population, to have effects on the DNA methylation status of specific genes in the placenta and thus supports a potentially novel mechanism for arsenic to affect long-term children's health.Green BB, Karagas MR, Punshon T, Jackson BP, Robbins DJ, Houseman EA, Marsit CJ. 2016. Epigenome-wide assessment of DNA methylation in the placenta and arsenic exposure in the New Hampshire Birth Cohort Study (USA). Environ Health Perspect 124:1253-1260; http://dx.doi.org/10.1289/ehp.1510437.
| S-EPMC4977055 | biostudies-literature
Project description:BackgroundStudies suggest that arsenic exposure influences birth outcomes; however, findings are mixed.ObjectiveWe assessed in utero arsenic exposure in relation to birth outcomes and whether maternal prepregnancy weight and infant sex modified the associations.MethodsAmong 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.ResultsMedian (interquartile range) of total urinary arsenic [tAs; inorganic arsenic (iAs) + monomethylarsonic acid (MMA) + dimethylarsinic acid (DMA)] was 3.4 ?g/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.ConclusionsLow-level arsenic exposure may affect fetal growth, and the associations may be modified by maternal weight status and infant sex.CitationGilbert-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.
| S-EPMC4977046 | biostudies-literature
Project description:As part of the New Hampshire Birth Cohort Study, children 3 to 5 years of age participated in a personal PM2.5 exposure study. This paper characterizes the personal PM2.5 exposure and protocol compliance measured with a wearable sensor. The MicroPEM™ collected personal continuous and integrated measures of PM2.5 exposure and compliance data on 272 children. PM2.5, black carbon (BC), and brown carbon tobacco smoke (BrC-ETS) exposure was measured from the filters. We performed a multivariate analysis of woodstove presence and other factors that influenced PM2.5, BC, and BrC exposures. We collected valid exposure data from 258 of the 272 participants (95%). Children wore the MicroPEM for an average of 46% of the 72-h period, and over 80% for a 2-day, 1-night period (with sleep hours counted as non-compliance for this study). Elevated PM2.5 exposures occurred in the morning, evening, and overnight. Median PM2.5, BC, and BrC-ETS concentrations were 8.1 μg/m3, 3.6 μg/m3, and 2.4 μg/m3. The combined BC and BrC-ETS mass comprised 72% of the PM2.5. Woodstove presence, hours used per day, and the primary heating source were associated with the children's PM2.5 exposure and air filters were associated with reduced PM2.5 concentrations. Our findings suggest that woodstove smoke contributed significantly to this cohort's PM2.5 exposure. The high sample validity and compliance rate demonstrated that the MicroPEM can be worn by young children in epidemiologic studies to measure their PM2.5 exposure, inform interventions to reduce the exposures, and improve children's health.
| S-EPMC8620988 | biostudies-literature
Project description:BackgroundWe have previously reported that in utero arsenic exposure is associated with increased length and other anthropometric outcomes at birth in a U.S. cohort. However, it is unknown whether these anthropometric differences persist through early life.ObjectivesWe assessed in utero arsenic exposure in relation to attained anthropometry and growth trajectories through the first year of life.MethodsAmong 760 mother-infant pairs from the New Hampshire Birth Cohort Study, we assessed in utero arsenic exposure using maternal second trimester urinary arsenic and assessed infant growth from medical records.ResultsMedian maternal second trimester total urinary arsenic (tAs; inorganic arsenic + monomethylarsonic acid + dimethylarsinic acid) was 3.96 μg/L (IQR: 2.02, 6.72). In adjusted linear mixed effects models, each doubling of maternal urinary tAs was associated with a 0.05 increase in length WHO Z score (95% CI: 0, 0.09) over the first year of life which corresponds to an approximately 0.12 cm increase in males and 0.13 cm increase in females at 12 months. No associations were observed between urinary tAs and attained weight, weight-for-length, or head circumference. In adjusted piecewise linear mixed effects models, each doubling of urinary tAs was associated with a 0.07 (95% CI: 0.02, 0.12) cm per month decreased length growth rate through 3.5 months with no evidence of an association thereafter. No associations were observed between urinary tAs and infant weight gain or change in weight-for-length and head circumference through one year.ConclusionsOn average, infants exposed to higher in utero arsenic attained modestly longer length during the first year, despite having slower linear growth in the first 3.5 months of life. This suggests that the previously demonstrated arsenic-associated longer length among study infants at birth persists through the first year of life. No other anthropometric associations with in utero arsenic exposure were observed across the full study population.
| S-EPMC7333643 | biostudies-literature
Project description:Arsenic exposure may alter the efficiency of DNA repair. UV damage is specifically repaired by nucleotide excision repair (NER), and common genetic variants in NER may increase risk for non-melanoma skin cancer (NMSC).We tested whether polymorphisms in the NER genes XPA (A23G) and XPD (Asp312Asn and Lys751Gln) modify the association between arsenic and NMSC.Incident cases of basal and squamous cell carcinoma (BCC and SCC, respectively) were identified through a network of dermatologists and pathology laboratories across New Hampshire. Population-based controls were frequency matched to cases on age and sex. Arsenic exposure was assessed in toenail clippings. The analysis included 880 cases of BCC, 666 cases of SCC, and 780 controls.There was an increased BCC risk associated with high arsenic exposure among those homozygous variant for XPA [odds ratio (OR) = 1.8; 95% confidence interval (CI), 0.9-3.7]. For XPD, having variation at both loci (312Asn and 751Gln) occurred less frequently among BCC and SCC cases compared with controls (OR = 0.8; 95% CI, 0.6-1.0) for both case groups. In the stratum of subjects who have variant for both XPD polymorphisms, there was a 2-fold increased risk of SCC associated with elevated arsenic (OR = 2.2; 95% CI, 1.0-5.0). The test for interaction between XPD and arsenic in SCC was of borderline significance (p < 0.07, 3 degrees of freedom).Our findings indicate a reduced NMSC risk in relation to XPD Asp312Asn and Lys751Gln variants. Further, these data support the hypothesis that NER polymorphisms may modify the association between NMSC and arsenic.
| S-EPMC1940098 | biostudies-literature
Project description:BackgroundChronic arsenic exposure has been associated with pregnancy complications and reduced fetal growth in populations where total arsenic exposure exceeds 50 μg/L. However, the potential effect on pregnancy outcomes remains unclear at lower levels of arsenic exposure, such as those most commonly observed in the United States.ObjectivesWe evaluated the associations between arsenic exposure during pregnancy with fetal growth and risk of pregnancy complications using data from mother-infant pairs participating in the National Children's Study.MethodsPrenatal arsenic exposure was measured using maternal urine collected during the third trimester. Information about pregnancy complications was abstracted from medical records. Fetal growth, including gestational age, birth weight, birth length, head circumference, and ponderal index, was ascertained through physical measurement at birth and extracted from medical records.ResultsMedians [interquartile range (IQR)] of maternal urinary total arsenic and dimethylarsinic acid (DMA) were 7.77 μg/L (7.98) and 3.44 μg/L (3.13), respectively. Each increase in IQR of prenatal total arsenic level was associated with greater birth length (+0.28 cm; 95% CI: 0.14, 0.42), greater head circumference (+0.12 cm; 95% CI: 0.04, 0.21), and lower ponderal index (-0.37 kg/m3; 95% CI: -0.58, -0.17). Similar results were obtained for levels of prenatal DMA. Tests for multiplicative interaction indicate that prenatal urinary DMA was negatively associated with gestational age among female infants (-0.44 week decrease in gestational age estimated for each IQR increase in DMA; 95% CI: -0.84, -0.05), while no association was observed among male infants (pinteraction = 0.02). No significant associations were detected between arsenic and birth weight or pregnancy complications.ConclusionsHigher prenatal arsenic exposure was associated with longer birth length, greater head circumference, and lower ponderal index. Associations between arsenic and gestational age may be modified by infant sex.
| S-EPMC7167354 | biostudies-literature
Project description:Background Early-life exposures during gestation may permanently alter thyroid physiology and health in adulthood. We investigated whether exposure to the Dutch Famine (1944-1945) in late, mid, or early gestation influences thyroid function (i.e., incidence of thyroid disease, thyroid autoantibodies, thyroid stimulating hormone (TSH), and free thyroxine (FT4) levels) in adulthood. We specifically assessed whether potential effects of famine differed for men and women. Methods This study includes 910 men and women born as term singletons in the Wilhelmina Gasthuis in Amsterdam, the Netherlands, shortly before, during, or after the Dutch Famine. We evaluated medical histories for previous diagnosis or current treatment for thyroid dysfunction. At age 50 blood samples were drawn from 728 individuals for tests of thyroid function. We studied the prevalence of overt hypo- and hyperthyroidism and thyroid autoimmunity using medical histories, and measurements of TSH, FT4, anti-TPO and anti-TG, comparing participants exposed to famine at different pregnancy trimesters or born before or conceived after the famine. Additionally, we studied associations of TSH and FT4 levels with in utero famine exposure in a subsample of men and women free of thyroid disease that were exposed in late, mid, or early gestation. Results There were no differences in thyroid dysfunction diagnosis or current treatment between participants at age 50 years who been exposed to famine during different periods of gestation and those born before or conceived after. There was no association between famine exposure and overt hypo- or hyperthyroidism or thyroid autoantibody positivity. Women who had been exposed to famine in mid gestation had slightly lower TSH levels than women who had not been exposed to famine prenatally (b=-0.06; 95%; CI=[-0.11,-0.02]; p<0.01). No differences in TSH levels were observed in men, and no differences in FT4 levels were observed in men or women. Conclusions There are no differences in adult thyroid disease at age 50 years according to prenatal famine exposure. However, the lower TSH levels in women exposed to famine in the second trimester suggest that there may be sex-specific effects of famine exposure during a critical period of thyroid development on hypothalamic-pituitary-thyroid axis regulation in adulthood.
| S-EPMC9280834 | biostudies-literature