Maternal-Infant Research On Environmental Chemicals Research Articles

Early prenatal use of a multivitamin diminishes the risk for inadequate vitamin D status in pregnant women: results from the Maternal-Infant Research on Environmental Chemicals (MIREC) cohort study

ABSTRACTBackgroundReports on the adequacy of vitamin D status of pregnant women are not available in Canada.ObjectivesThe objectives of this study were to examine vitamin D status across pregnancy and identify the correlates of vitamin D status of pregnant women in Canada.MethodsPregnant women (≥18 years) from 6 provinces (2008–2011) participating in a longitudinal cohort were studied. Sociodemographic data, obstetrical histories, and dietary and supplemental vitamin D intakes were surveyed. Plasma 25-hydroxyvitamin D (25OHD) was measured using an immunoassay standardized to LC-MS/MS from samples collected during the first (n = 1905) and third trimesters (n = 1649) and at delivery (n = 1543). The proportion of women with ≥40 nmol/L of plasma 25OHD (adequate status) was estimated at each time point, and factors related to achieving this cut point were identified using repeated-measures logistic regression. Differences in 25OHD concentrations across trimesters and at delivery were tested a using repeated-measures ANOVA with a post hoc Tukey's test.ResultsIn the first trimester, 93.4% (95% CI: 92.3%–94.5%) of participants had 25OHD ≥40 nmol/L. The mean plasma 25OHD concentration increased from the first to the third trimester and then declined by delivery (69.8 ± 0.5 nmol/L, 78.6 ± 0.7 nmol/L, and 75.7 ± 0.7 nmol/L, respectively; P < 0.0001). A lack of multivitamin use early in pregnancy reduced the odds of achieving 25OHD ≥40 nmol/L (ORadj = 0.33; 95% CI: 0.25–0.42) across all time points. Factors associated with not using a prenatal multivitamin included multiparity (ORadj = 2.08; 95% CI: 1.42–3.02) and a below-median income (ORadj = 1.39; 95% CI: 1.02–1.89).ConclusionsThe results from this cohort demonstrate the importance of early multivitamin supplement use to achieve an adequate vitamin D status in pregnant women.

Associations Between Prenatal Fluoride Exposure and Performance IQ in Canadian Preschool Aged Children: A Multilevel Modeling Approach

BACKGROUND AND AIM: Prenatal fluoride exposure is associated with reduced IQ in children, especially Performance IQ (PIQ; nonverbal intelligence), but studies have not accounted for hierarchical clustering. We examined the association between sex-specific prenatal fluoride exposure and PIQ using multilevel modeling (MLM) to account for nesting of 448 mother-child pairs within 184 postal codes and six cities. METHODS: Our sample was from the Maternal-Infant Research on Environmental Chemicals (MIREC) prospective Canadian birth cohort. Variables included maternal urinary fluoride (MUF; adjusted for dilution), PIQ scores at age 3-4 years from the WPPSI, and participant level covariates (HOME scores, maternal education level, and maternal race). A series of three-level MLMs were fit to estimate associations between within-postal code and within-city centered MUF and PIQ. RESULTS:Median MUF concentration was 0.44 mg/L (IQR= 0.35), with average PIQ of 102 (SD= 14) for boys and 105 (SD= 14) for girls. A three-level intra-class correlation revealed that 3.8% and 9.1% of the variance in PIQ was accounted for by nesting of dyads in postal codes and cities, respectively. The interaction between child sex and MUF and the covariate effects were fixed across postal codes and cities in the optimal model. The interaction between child sex and within-postal-code MUF was significant (p .05).For boys, a 1 mg/L increase in within-postal-code MUF was significantly associated with PIQ, B= -7.9 (95% CI: -13.6, -2.2); for girls, the association was not significant, B= 1.7 (95% CI: -5.0, 8.5). Centering MUF within city resulted in a weaker effect among boys (B= -5.7 95% CI: -10.2, -1.2), and a stronger, but nonsignificant effect among girls (B= 3.3, 95% CI: -2.7, 9.3). CONCLUSIONS:For boys, the stronger effect of MUF in postal codes than cities shows the importance of accounting for hierarchical clustering in the MIREC cohort to examine associations between prenatal fluoride exposure and PIQ. KEYWORDS: biomarkers of exposure, children’s environmental health, epidemiology, fluoride, neurodevelopmental outcomes

Prenatal Fluoride Exposure and Autism Spectrum Disorder-Like Behaviors in a Sample of Canadian Preschool Aged Children: The MIREC Study

BACKGROUND AND AIM: A growing body of evidence indicates that prenatal exposure to fluoride is neurotoxic to child development. However, epidemiologic research examining fluoride’s effect on autism spectrum disorder (ASD) is lacking. Our aim was to examine the association of prenatal fluoride exposure with ASD-like behaviors in a sample of preschool aged children living in regions with fluoridated and non-fluoridated community water. METHODS: We analyzed 502 mother-child pairs from the Maternal-Infant Research on Environmental Chemicals (MIREC), a prospective multicentered Canadian birth cohort, with available data on prenatal fluoride exposure, ASD-like behaviors, and covariates. We measured fluoride exposure by averaging maternal urinary fluoride adjusted for specific gravity (MUFsg) across three trimesters. We assessed children’s ASD-like behaviors at 3-4 years of age using the parent-reported Social Responsiveness Scale-2 (SRS-2) Preschool Form, with higher scores indicating more behavioral symptomology. Covariate adjusted linear and quantile regression models were used to estimate the difference in the relationship between MUFsg and SRS-2 conditional mean and quantile subscale T-scores, respectively. We adjusted all regression models for baseline maternal age, second-hand smoke, marital status, parity, child sex, study site, and the HOME score that was assessed at child follow-up visit. RESULTS:Mean MUFsg concentration was 0.53 mg/L (SD=0.38), and mean SRS-2 Total T-score was 45.3 (SD=6.2). In multiple linear regression, a 1 mg/L increase in MUFsg concentration was not statistically associated with SRS-2 Total T-score (β=0.12; 95% CI, -1.36, 1.60; P=0.87). Likewise, we observed no statistical association for all other SRS-2 subscale T-scores. In quantile regression, there was no statistical association between MUFsg and SRS-2 Total T-score across percentiles: 0.1, 0.3, 0.5, 0.7 and 0.9. Effect modification by sex was not observed. CONCLUSIONS:In this Canadian cohort, we found no evidence of a statistical association between prenatal fluoride exposure and ASD-like behaviors among preschool aged children. KEYWORDS: biomarkers of exposure, children’s environmental health, epidemiology, fluoride, neurodevelopmental outcomes

A Benchmark Dose Analysis for Maternal Pregnancy Urine-Fluoride and IQ in Children.

As a guide to establishing a safe exposure level for fluoride exposure in pregnancy, we applied benchmark dose modeling to data from two prospective birth cohort studies. We included mother-child pairs from the Early Life Exposures in Mexico to Environmental Toxicants (ELEMENT) cohort in Mexico and the Maternal-Infant Research on Environmental Chemicals (MIREC) cohort in Canada. Maternal urinary fluoride concentrations (U-F, in mg/L, creatinine-adjusted) were measured in urine samples obtained during pregnancy. Children were assessed for intelligence quotient (IQ) at age 4 (n = 211) and between six and 12 years (n = 287) in the ELEMENT cohort, and three to four years (n = 407) in the MIREC cohort. We calculated covariate-adjusted regression coefficients and their standard errors to assess the association of maternal U-F concentrations with children's IQ measures. Assuming a benchmark response of 1 IQ point, we derived benchmark concentrations (BMCs) and benchmark concentration levels (BMCLs). No deviation from linearity was detected in the dose-response relationships, but boys showed lower BMC values than girls. Using a linear slope for the joint cohort data, the BMC for maternal U-F associated with a 1-point decrease in IQ scores was 0.31 mg/L (BMCL, 0.19 mg/L) for the youngest boys and girls in the two cohorts, and 0.33 mg/L (BMCL, 0.20 mg/L) for the MIREC cohort and the older ELEMENT children. Thus, the joint data show a BMCL in terms of the adjusted U-F concentrations in the pregnant women of approximately 0.2 mg/L. These results can be used to guide decisions on preventing excess fluoride exposure in pregnant women.

Prenatal exposure to endocrine disrupting chemical mixtures and infant birth weight: A Bayesian analysis using kernel machine regression

BackgroundPregnant women are regularly exposed to a multitude of endocrine disrupting chemicals (EDCs). EDC exposures, both individually and as mixtures, may affect fetal growth. The relationship of EDC mixtures with infant birth weight, however, remains poorly understood. We examined the relations between prenatal exposure to EDC mixtures and infant birth weight. MethodsWe used data from the Maternal-Infant Research on Environmental Chemicals (MIREC) Study, a pan-Canadian cohort of 1857 pregnant women enrolled between 2008 and 2011. We quantified twenty-one chemical concentrations from five EDC classes, including organochlorine compounds (OCs), metals, perfluoroalkyl substances (PFAS), phenols and phthalate metabolites that were detected in >70% of urine or blood samples collected during the first trimester. In our primary analysis, we used Bayesian kernel machine regression (BKMR) models to assess variable importance, explore EDC mixture effects, and identify any interactions among EDCs. Our secondary analysis used traditional linear regression to compare the results with those of BKMR and to quantify the changes in mean birth weight in relation to prenatal EDC exposures. ResultsWe found evidence that mixtures of OCs and metals were associated with monotonic decreases in mean birth weight across the whole range of exposure. trans-Nonachlor from the OC mixture and lead (Pb) from the metal mixture had the greatest impact on birth weight. Our linear regression analysis corroborated the BKMR results and found that a 2-fold increase in trans-nonachlor and Pb concentrations reduced mean birth weight by −38 g (95% confidence interval (CI): −67, −10) and −39 g (95% CI: −69, −9), respectively. A sex-specific association for OC mixture was observed among female infants. PFAS, phenols and phthalates were not associated with birth weight. No interactions were observed among the EDCs. ConclusionsUsing BKMR, we observed that both OC and metal mixtures were associated with decreased birth weight in the MIREC Study. trans-Nonachlor from the OC mixture and Pb from the metal mixture contributed most to the adverse effects.

Associations between Urinary, Dietary, and Water Fluoride Concentrations among Children in Mexico and Canada.

Fluoride, which may be toxic to the developing brain, is added to salt in Mexico and drinking water in Canada to prevent dental caries. We compared childhood urinary fluoride (CUF) concentrations in Mexico City and Canada to characterize patterns of fluoride exposure in these two populations. We also examined associations of CUF with dietary and water fluoride levels in Mexico City and Canada respectively. We included 561 children (ages 4–6; mean age 4.8 years) from the Programming Research in Obesity, Growth, Environment, and Social Stress (PROGRESS) cohort in Mexico City, and 645 children (ages 2–6; mean age 3.7 years) from the Maternal–Infant Research on Environmental Chemicals (MIREC) cohort in Canada. We applied Spearman correlations, T-tests, ANOVA or covariate-adjusted linear regression to examine associations of CUF (mg/L; adjusted for specific gravity) with demographics and dietary or water fluoride concentrations. We used Welch equivalence testing to compare means across cohorts. Mean (SD) CUF was equivalent (t = 4.26, p < 0.001) in PROGRESS: 0.74 (0.42) and fluoridated Canadian communities: 0.66 (0.47), but lower in non-fluoridated Canadian communities: 0.42 (0.31) (t = −6.37, p < 0.001). Water fluoride concentrations were significantly associated with CUF after covariate adjustment for age and sex in MIREC (B = 0.44, 95% CI: 0.30, 0.59, p < 0.001). In contrast, daily food and beverage fluoride intake was not associated with CUF in PROGRESS (p = 0.82). We found that CUF levels are comparable among children in Mexico City and fluoridated Canadian communities, despite distinct sources of exposure. Community water fluoridation is a major source of fluoride exposure for Canadian children.

Urinary fluoride patterns among children in Mexico and Canada

Background: New research suggesting fluoride is a developmental neurotoxicant highlights the importance of characterizing fluoride exposure in children. Fluoride is added to salt in Mexico and to drinking water in Canada to prevent dental caries. We examined the association of childhood urinary fluoride (CUF) with food and water fluoride levels in Mexico and Canada, respectively. Methods: We included 551 children (ages 4-6) from the Programming Research in Obesity, Growth, Environment and Social Stress (PROGRESS) cohort in Mexico City, and 522 children (ages 2-6) from the Maternal-Infant Research on Environmental Chemicals (MIREC) cohort in Canada. We applied Spearman correlations, T-tests or covariate adjusted linear regression to examine associations of CUF (mg/L; adjusted for specific gravity) with demographics and food or water fluoride concentrations. We used equivalence testing to compare cohort means. Results: Median (IQR) CUF concentrations were 0.67 (0.36) in PROGRESS, 0.56 (0.76) in fluoridated Canadian communities, and 0.35 (0.53) in non-fluoridated Canadian communities. Mean+/-SD CUF was equivalent in PROGRESS (0.74+/-0.42) and fluoridated Canadian communities (0.79+/-0.71), but lower in non-fluoridated Canadian communities (0.55+/-0.60, t (276)=-6.02, p≤.001). CUF tended to increase with age in PROGRESS (ρ=.10, p=.02) and MIREC (ρ=.17, p≤.001). In MIREC, CUF was higher in males (0.79+/-0.74) than females (0.54+/-0.58, p&lt;.001); however, no sex differences were observed in PROGRESS (p=.97). In MIREC, water fluoride concentrations (median=0.2 mg/L) were significantly associated with CUF after covariate adjustment for age and sex (B=0.36, 95%CI: 0.11, 0.61, p=.005). Daily food and beverage fluoride intake (median=624.41 mcg/day) was not associated with CUF in PROGRESS (p=.89). Conclusion: Our findings suggest that the magnitude of fluoride exposure is comparable among children in Mexico City and fluoridated Canadian communities, despite different sources of exposure. Further studies are needed to clarify whether higher CUF among older children reflects different exposure patterns, sources of exposure or age-related toxicokinetics. Keywords: Fluoride, exposure, intake, development, epidemiology.

Relationships between measures of ambient air pollution and markers of inflammation during pregnancy

Background Outdoor air pollution can influence important biological processes such as inflammation, and has been shown to increase the risk of adverse pregnancy and birth outcomes. Pregnancy-specific biological processes, such as increased estrogen production and altered metabolism can impair the body’s ability to detoxify air pollution exposures, highlighting the need to study exposures during pregnancy. We examined the relationship between ambient PM2.5 and NO2, with markers of inflammation during pregnancy in a cohort of Canadian women.Methods We analyzed data from 1,397 women enrolled in the Maternal-Infant Research on Environmental Chemicals (MIREC) study, a Canadian pregnancy cohort. Residential PM2.5 and NO2 exposures were estimated using satellite-based and land-use regression models to generate overall pregnancy, and trimester specific averages. Inflammatory markers including C-reactive protein (CRP), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumour Necrosis Factor alpha (TNFα) were measured in third-trimester maternal plasma samples. Multivariable linear regression was used to estimate the effects of an inter-quartile (IQR) change in both PM2.5 and NO2 on markers of inflammation, while adjusting for relevant individual-level confounders, including maternal behaviours, and established predictors of inflammation.Results An IQR (5.42 μg/m3) change in PM2.5 exposure during pregnancy was associated with higher IL-8 levels in the third trimester (5.13% [95% CI: 0.60% – 10.74%]). Exposure to PM2.5 and NO2 (IQR: 19.17ppb) during pregnancy was not significantly associated with other inflammatory makers. Additional analyses examining trimester-specific exposures, non-linear dose-response relationships, and quantitative bias will also be presented.Conclusions We showed that average exposure to PM2.5 during pregnancy was associated with increased third-trimester IL-8 levels, suggesting a possible mechanism through which air pollution exposures may impact the risk of adverse pregnancy and birth outcomes. This work adds to the limited literature on the impact of air pollution on inflammation during pregnancy in a low-exposure cohort.

Temporal variation of total mercury levels in the hair of pregnant women from the Maternal-Infant Research on Environmental Chemicals (MIREC) study

Prenatal exposure to total mercury (T-Hg) comes from both natural and anthropogenic sources. T-Hg can cross the blood-brain and placental barriers, and may be associated with future neurological and physiological dysfunctions. Scalp hair is an optimal and non-invasive indicator of chronic T-Hg exposure. As part of the Maternal-Infant Research on Environmental Chemicals (MIREC) Study, hair samples from 350 women were collected within weeks after giving birth, to determine temporal variations in T-Hg levels from preconception to delivery, and to compare these levels to corresponding levels measured in other matrices (maternal and umbilical cord blood, and infant’s meconium). A maximum of 12 one-cm hair segments were cut starting at the scalp; segments closer to the scalp reflected recent exposure (within the last month). For proper comparison, the hair segments were matched with the collection dates for other matrices. GM hair T-Hg levels greatly decreased during pregnancy, from 0.26 μg g−1 (preconception or full-length hair) to 0.18 μg g−1 (at delivery or segments closer to the scalp). A similar decreasing trend was found for T-Hg in maternal blood: 1st trimester (0.60 μg L−1) to 3rd trimester (0.47 μg L−1). The median hair-to-blood ratios of T-Hg levels varied from 364 (1st trimester), to 408 (3rd trimester), to 229 (cord blood). Very low T-Hg levels were detected in meconium. Mercury levels in blood and hair correlated with consumption of large predatory fish.

Associations of prenatal urinary phthalate exposure with preterm birth: the Maternal-Infant Research on Environmental Chemicals (MIREC) Study.

To examine the relation between prenatal urinary phthalate metabolite concentrations and preterm birth (PTB). The data were drawn from the Maternal-Infant Research on Environmental Chemicals (MIREC) Study, a pan-Canadian cohort of 1857 pregnant women enrolled between 2008 and 2011. We quantified urinary concentrations of 7 phthalate metabolites that were detected in > 70% of urine samples collected during the first trimester. Gestational age was obtained from either the last menstrual period or early ultrasound. We used Cox proportional hazard models to examine the associations of urinary phthalate metabolite concentrations, plus the molar sum of di-2-ethylhexyl phthalate metabolites (∑DEHP), with time to delivery before 37weeks of gestation. We also examined PTB by clinical presentation. PTBs presented with either spontaneous labour or premature rupture of the membrane were considered spontaneous PTB (sPTB). Additionally, we used multiple linear regression to model changes in mean gestational age in relation to phthalate exposure. We found no evidence of an association between first trimester phthalate metabolite concentrations and PTB among the MIREC study participants. For example, each 2-fold increase in any of the 7 phthalate concentrations or ∑DEHP was associated with hazard ratios (HRs) for PTB ranging from 0.95 to 1.07 with 95% confidence intervals including the null. An assessment of non-linear trends showed some evidence of non-monotonic dose-response relationships between phthalates and PTB. Furthermore, male infants exposed to MCPP showed higher sPTB risk compared with female infants. Phthalate exposure during early pregnancy is not clearly associated with the risk of PTB among this Canadian population.

Prenatal exposure to legacy contaminants and visual acuity in Canadian infants: a maternal-infant research on environmental chemicals study (MIREC-ID)

BackgroundPrenatal exposure to environmental contaminants can have deleterious effects on child development. While psychomotor, cognitive and behavioural outcomes have been investigated in relation to chronic exposure, the associations with visual functions remains unclear. The present study’s aim was to assess the associations of prenatal exposure to legacy persistent organic pollutants and heavy metals with visual acuity in Canadian infants. The potential protective effects of selenium against mercury toxicity were also examined.MethodsParticipants (mean corrected age = 6.6 months) were part of the Maternal-Infant Research on Environmental Chemicals (MIREC) study. Concentrations of polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), lead and mercury were measured in maternal blood during pregnancy, as well as in the cord blood. The Teller acuity card test (TAC) (n = 429) and the visual evoked potentials in a sub-group (n = 63) were used to estimate behavioural and electrophysiological visual acuity, respectively. Multivariable linear regression models were used to investigate the relationship between exposure to each contaminant and visual acuity measures, while controlling for potential confounders. Breastmilk selenium, which was available for about half of the TAC and VEP samples, was also taken into account in the mercury models as exploratory analyses.ResultsWe observed no significant associations between exposure to any contaminants and TAC. Analyses revealed a negative trend (p values < 0.1) between cord blood lead and mercury and electrophysiological visual acuity, whereas PCB and PBDE showed no association. When adding breastmilk selenium concentration to the mercury models, this association became statistically significant for cord concentrations (β = − 3.41, 95% CI = − 5.96,-0.86), but also for blood levels at 1st and 3rd trimesters of pregnancy (β = − 3.29, 95% CI = − 5.69,-0.88). However, further regression models suggested that this change in estimates might not be due to adjustment for selenium, but instead to a change in the study sample.ConclusionsOur results suggest that subtle, but detectable alterations of infant electrophysiological visual acuity can be identified in a population prenatally exposed to low mercury concentrations. Compared to behavioural visual acuity testing, electrophysiological assessment may more sensitive in detecting visual neurotoxicity in relation with prenatal exposure to mercury.

Fluoride Exposure from Infant Formula and Child IQ in a Canadian Birth Cohort

OPS 36: Health effects of dietary exposures, Room 210, Floor 2, August 27, 2019, 4:30 PM - 5:30 PM Background: Consumption of infant formula reconstituted with fluoridated water can lead to excessive intake of fluoride in infants. We examined the association between water fluoride concentration and intellectual ability (IQ) among preschool children who lived in fluoridated or non-fluoridated cities in Canada and were either formula-fed or breastfed during the first six months after birth. Methods: We measured water fluoride concentration using municipal water reports matched to the child’s birthdate to six-months of age. We restricted our analyses to 398 mother-child dyads enrolled in the Maternal-Infant Research on Environmental Chemicals (MIREC) cohort who reported drinking tap water. We evaluated Full Scale IQ (FSIQ) using the Wechsler Primary and Preschool Scale of Intelligence-III at 3 to 4 years. We used multiple linear regression analyses with an interaction to examine how the covariate-adjusted association between water fluoride concentration and FSIQ scores differs according to feeding status. In secondary analyses, we controlled for prenatal fluoride exposure. Results: Thirty-eight percent of mother-child dyads lived in communities supplied with fluoridated municipal water. An increase of 0.5 mg/L fluoride concentration (the difference between fluoridated and non-fluoridated region) corresponded to a drop of 4.4 FSIQ points (95% CI: -8.34, -0.46, p=.03) in the formula-fed group. In contrast, this relationship was not significant in the breastfed group (B=-1.34, 95% CI: -5.04, 2.38, p=.48). Controlling for prenatal fluoride exposure weakened the association between water fluoride concentration and FSIQ in the formula-fed group (B=-3.88, 95% CI = -8.12, 0.37, p=.07). Conclusions: The results, which indicate that fluoride concentration in drinking water was associated with lower FSIQ in children who were formula fed, underscore the need to reduce the use of fluoridated water to reconstitute formula during infancy.

Perchlorate in human milk samples from the maternal-infant research on environmental chemicals study (MIREC)

ABSTRACTPerchlorate is a low molecular weight highly soluble anion. It occurs naturally in the environment, primarily near potash deposits and in arid regions. The determination of perchlorate in human milk is of interest in vulnerable populations such as infants and pregnant women. In this study, a sensitive and selective isotope dilution ion chromatography/tandem mass spectrometry (ID IC-MS/MS) method was developed and validated for the determination of perchlorate in human milk samples collected from the Maternal-Infant Research on Environmental Chemicals (MIREC) Study. The limit of detection (LOD) was 0.27 µg·kg−1 for human milk. A total of 439 human milk samples were analysed with measurable levels of perchlorate in most of the milk samples, and the mean value was 7.62 ± 32.7 µg·kg−1. This project provided important information related to perchlorate levels in human milk collected across Canada and the extent to which pregnant women and their infants may be exposed to perchlorate. A dietary exposure assessment was also conducted in infants based on the measured values in human milk. The mean perchlorate probable daily intakes (PDIs) for infants consuming human milk were 0.31 ± 0.07 μg/kg bw/day for infants under 1 year and 0.17 ± 0.10 μg/kg bw/day for infants between 1 and 3 years old. None of the estimates exceeded the FAO/WHO provisional maximum tolerable daily intake (PMTDI) of 10 μg/kg bw/day.

Blood metal levels and early childhood anthropometric measures in a cohort of Canadian children

Fetal exposure to some toxic metals has been associated with reduced fetal growth, but the impact of contemporary, low-level metals on anthropometric measures in childhood is not well understood. Our primary objective was to quantify associations between childhood levels of toxic metals and concurrently measured body mass index (BMI) in a population of Canadian preschool-aged children.We collected biomonitoring data and anthropometric measures on 480 children between the ages of two and five years in the Maternal-Infant Research on Environmental Chemicals (MIREC) Child Development Plus study. Concentrations of four toxic metals (lead, arsenic, cadmium, and mercury) were measured in whole blood collected from pregnant women and their children. Blood levels of key essential elements were also measured in children. Children's weight, height, and BMI z-scores were calculated using the World Health Organization growth standards. We used a series of linear regression models, adjusted for potential parental confounders, concurrently measured metals and elements, and prenatal blood metal levels, to evaluate associations between tertiles of each toxic metal and anthropometric measures. We tested for effect modification by sex.Of the 480 children, 449 (94%) were singleton births and had complete biomonitoring and anthropometric data. The majority of children had detectable concentrations of metals. In the adjusted models, girls with blood lead concentrations in the highest tertile (>0.82 μg/dL) had, on average, 0.26 (95% Cl: -0.55, 0.03) lower BMI z-scores than those in the referent category. In contrast, boys with lead levels in the highest tertile had, on average, 0.14 higher BMI z-scores (95% Cl: -0.14, 0.41) (p-value heterogeneity = 0.04).In this population of Canadian preschool-aged children with low-level blood lead concentrations, we observed effect modification by sex in the association between Pb and BMI but no statistically significant associations in the sex-specific strata. Child blood levels of As, Cd, and Hg were not associated with childhood BMI, weight, or height in boys or girls.

The MTHFR 677C>T polymorphism is associated with unmetabolized folic acid in breast milk in a cohort of Canadian women

Maternal nutrition and genetics are determinants of breast-milk nutrient composition and, as such, are determinants of the nutritional exposure of breastfed infants. The aim of this study was to determine whether common maternal single nucleotide polymorphisms (SNPs) in folate-dependent enzymes are associated with breast-milk folate content in a cohort of mothers enrolled in the Maternal-Infant Research on Environmental Chemicals (MIREC) study. The MIREC study is a Canadian prospective pregnancy cohort study that recruited 2001 participants between 2008 and 2011. Five folate-related SNPs-MTHFR 677C>T (rs1801133), MTHFR 1298A>C (rs1801131), MTHFR 1793G>A (rs2274976), MTR 2756A>G (rs1805087), and MTRR 66A>G (rs1801394)-were genotyped. Breast milk was sampled ∼1 mo postpartum, and tetrahydrofolate (THF), 5-methyl-THF, 5-formyl-THF, 5,10-methenyl-THF, and unmetabolized folic acid (UMFA) were measured using liquid chromatography-tandem mass spectrometry in a subset of participants (n=551). Associations were assessed using Wald's test. Associations were considered significant if P≤0.01 (Bonferroni correction for multiple testing). None of the SNPs were associated with total breast-milk folate. However, the MTHFR 677C>T SNP was associated with breast-milk UMFA (R2=0.01; unadjusted P=0.004), explaining a small portion of total variance; this association remained significant when adjusted for other covariates, including supplemental folic acid consumption. The MTHFR 1793G>A and MTRR 66A>G SNPs tended to be associated with 5-methyl-THF (R2=0.008, P=0.04) and reduced folates (THF+5-methyl-THF+5-formyl-THF+5,10-methenyl-THF; R2=0.01, P=0.02), respectively. We found that total breast-milk folate content was not associated with any of the folate-related SNPs examined. The association between the MTHFR 677C>T SNP and breast-milk UMFA, albeit modest, highlights the need to better understand the determinants of breast-milk folate and the impact they might have on milk folate bioavailability.

Prevalence of Fetal Alcohol Exposure by Analysis of Meconium Fatty Acid Ethyl Esters; A National Canadian Study

Our study aimed to estimate the prevalence of heavy fetal alcohol exposure through the analysis of meconium FAEEs as an objective biomarker of fetal exposure. We conducted a study on meconium samples collected nationwide through the Maternal-Infant Research on Environmental Chemicals (MIREC) Study Group. FAEE in meconium was quantified by an established headspace solid-phase microextraction coupled with gas chromatography-mass spectrometry (SPME GC-MS). Out of 1315 samples collected in 10 Canadian obstetric units coast to coast between 2008-2011, the estimated prevalence of positive meconium FAEE ranged between 1.16% and 2.40%, translating into at least 1800 new cases of FASD in Canada each year. Positive maternal self- reports of heavy alcohol use were tenfold lower (0.24%). Use of meconium FAEE revealed tenfold more cases of heavy exposure to maternal drinking than did maternal reports. The use of objective measures of maternal alcohol exposure is critical in accurately estimating risks and in monitoring effective prevention of FASD.

Assessing the Relation between Plasma PCB Concentrations and Elevated Autistic Behaviours using Bayesian Predictive Odds Ratios.

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by impaired social communication and repetitive or stereotypic behaviours. In utero exposure to environmental chemicals, such as polychlorinated biphenyls (PCBs), may play a role in the etiology of ASD. We examined the relation between plasma PCB concentrations measured during pregnancy and autistic behaviours in a subset of children aged 3–4 years old in the Maternal-Infant Research on Environmental Chemicals (MIREC) Study, a pregnancy and birth cohort of 546 mother-infant pairs from Canada (enrolled: 2008–2011). We quantified the concentrations of 6 PCB congeners that were detected in >40% of plasma samples collected during the 1st trimester. At age 3–4 years, caregivers completed the Social Responsiveness Scale-2 (SRS), a valid and reliable measure of children’s reciprocal social and repetitive behaviours and restricted interests. We examined SRS scores as both a continuous and binary outcome, and we calculated Bayesian predictive odds ratios for more autistic behaviours based on a latent variable model for SRS scores >60. We found no evidence of an association between plasma PCB concentrations and autistic behaviour. However, we found small and imprecise increases in the mean SRS score and odds of more autistic behaviour for the highest category of plasma PCB concentrations compared with the lowest category; for instance, an average increase of 1.4 (95%PCI: −0.4, 3.2) in the mean SRS (exposure contrast highest versus lowest PCB category) for PCB138 translated to an odds ratio of 1.8 (95%PCI: 1.0, 2.9). Our findings illustrate the importance of measuring associations between PCBs and autistic behaviour on both continuous and binary scales.

Associations between Maternal Exposure to Bisphenol A or Triclosan and Gestational Hypertension and Preeclampsia: The MIREC Study.

Little is known about the association between bisphenol A (BPA) or triclosan (TCS) exposure and hypertension in pregnancy. To investigate potential associations between maternal urinary concentrations of BPA or TCS and gestational hypertension (GH) and preeclampsia. Among 1,909 pregnant women participating in the maternal-infant research on environmental chemicals (MIREC) study, urinary concentrations of BPA and TCS were measured in the first trimester by liquid chromatography-tandem mass spectrometry using isotope dilution. Blood pressure was measured during each trimester. Multinomial regression was performed to estimate the adjusted odds ratio (aOR) and 95% confidence intervals (CI) for the associations between these phenols and GH and preeclampsia. BPA and TCS were not associated with GH or preeclampsia. However, in multiparous women, BPA (0.50-1.30 µg/L) was associated with decreased risk of GH (aOR =0.45; 95%CI: 0.21-0.98) while among nulliparous women, TCS was associated with an increased risk of GH (3.60-32.60 µg/L; aOR = 2.58; 95% CI: 1.09-6.13 and > 32.60 µg/L: aOR = 2.74; 95% CI: 1.15-6.51). BPA and TCS urinary concentrations were not associated with GH or preeclampsia; however, our results suggest an association between TCS and GH in nulliparous women. Additional studies are required to confirm our results.

Prenatal, concurrent, and sex-specific associations between blood lead concentrations and IQ in preschool Canadian children

BackgroundLead exposure predicts altered neurodevelopment and lower intelligence quotient (IQ) in children, but few studies have examined this association in children who have relatively low blood lead concentrations. ObjectivesTo test the associations between blood lead concentrations and cognitive function in Canadian preschoolers, with a possible moderation by sex. MethodsThe data were gathered from 609 mother-child pairs from the Maternal–Infant Research on Environmental Chemicals (MIREC) Study. Lead was measured in umbilical and maternal blood, and in children's venous blood at age 3–4 years. Cognitive function was measured with the Wechsler Preschool and Primary Scale of Intelligence (WPPSI-III) at 3–4 years. We tested the relationship between WPPSI-III scores and blood lead concentrations with multiple linear regression, adding child sex as a moderator. ResultsMedian blood lead concentrations for the mother at 1st trimester and 3rd trimester of pregnancy, and for cord and child blood were 0.60 μg/dL, 0.58 μg/dL, 0.79 μg/dL and 0.67 μg/dL, respectively. We found no association between cord blood lead concentrations and WPPSI-III scores in multivariable analyses. However, cord blood lead concentrations showed a negative association with Performance IQ in boys but not in girls (B = 3.44; SE = 1.62; 95% CI: 0.82, 5.98). No associations were found between WPPSI-III scores and prenatal maternal blood or concurrent child blood lead concentrations. ConclusionsPrenatal blood lead concentrations below 5 μg/dL were still associated with a decline in cognitive function in this Canadian cohort, but only for boys.

Time-to-pregnancy and offspring finger-length ratio (2D:4D).

Time-to-Pregnancy (TTP) is an epidemiological tool to assess couple fecundity. The finger digit ratio (2D:4D) has been suggested as a marker of androgen exposure in utero. Maternal, paternal, or couple-mediated factors related to fecundity may also have an effect on androgen exposure during pregnancy. We aimed to investigate the association between TTP, infertility, or use of Assisted Reproductive Technologies (ART) and offspring 2D:4D. Data from 673 mother-child pairs were collected from questionnaires in the Maternal-Infant Research on Environmental Chemicals (MIREC) study across 10 cities in Canada. The mean maternal age was 33.4 years (SD 4.7), with a median gestational age of 12.1 weeks (SD 1.3), at the time of recruitment. Our study included 338 girls and 335 boys, and the mean age of the children at follow-up was 3.5 years (SD 1.0). TTP was assessed through questionnaires during the first trimester of pregnancy. Digital photographs of both hands were taken in a follow-up study to calculate the children's 2D:4D (2-5 years). anova, t tests, and multiple linear regression analyses were conducted. Boys had significantly lower mean 2D:4Ds (0.936 ±0.041 in right hand, 0.936 ±0.040 in left hand) compared to girls (0.948 ±0.038 in right hand, 0.945 ±0.038 in left hand). The mean 2D:4D did not differ according to TTP, infertility, or use of ART. The only factors associated with the child's 2D:4D were the child's age and maternal 2D:4D. Our study does not support an association between TTP, infertility, or use of ART and children's 2D:4D.