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Children are exposed to many trace elements throughout their development. Given their ubiquity and potential to have effects on children's neurodevelopment, these exposures are a public health concern. This study sought to identify trace element mixture‐associated deficits in learning behavior using operant testing in a prospective cohort. We included 322 participants aged 6–7 years recruited in Mexico City with complete data on prenatal trace elements measurements (third trimester blood lead and manganese levels, and & urine cadmium and arsenic levels), demographic covariates, and the Incremental Repeated Acquisition (IRA), an associative learning task. Weighted quantile sum (WQS) regression models were used to estimate the joint association of the mixture of all four trace elements and IRA performance. Performance was adversely impacted by the mixture, with different elements relating to different aspects of task performance suggesting that prenatal exposure to trace element mixtures yields a broad dysregulation of learning behavior. [ABSTRACT FROM AUTHOR]

Phthalates are endocrine disrupting chemicals that may influence weight status; however, few studies have considered weight gain during pregnancy and subsequent long-term weight changes in women. To determine associations of prenatal phthalate exposure with maternal weight during pregnancy and through up to seven years post-delivery. We analyzed 15 urinary phthalate biomarker concentrations during the 2nd and 3rd trimesters among 874 pregnant women enrolled in the Programming Research in Obesity, Growth Environment and Social Stress Study in Mexico City. We examined three time-specific maternal weight outcomes: gestational weight gain (between 2nd and 3rd trimesters), short-term weight (between 3rd trimester and 12 months post-delivery), and long-term weight (between 18 months and 6–7 years post-delivery). We used Bayesian Kernel Machine Regression (BKMR) to estimate associations for the total phthalate mixture, as well as multivariable linear mixed models for individual phthalate biomarkers. As a mixture, 2nd trimester urinary phthalate biomarker concentrations were associated with somewhat lower gestational weight gain between the 2nd and 3rd trimesters (interquartile range, IQR, difference: −0.07 standard deviations, SD; 95% credible interval, CrI: −0.20, 0.06); multivariable regression and BKMR models indicated that this inverse association was primarily driven by mono-2-ethyl-5-carboxypentyl terephthalate (MECPTP). Prenatal (2nd and 3rd trimesters) urinary phthalate mixture concentrations were positively associated with maternal weight change through 12 months postpartum (IQR difference: 0.11 SD; 95% CrI: 0.00, 0.23); these associations persisted from 18 months to 6–7 years follow-up (IQR difference: 0.07 SD; 95% CrI: 0.04, 0.10). Postpartum weight changes were associated with mono-3-carboxypropyl phthalate (MCPP) and MECPTP. Prenatal phthalate exposure was inversely associated with gestational weight gain and positively associated with long-term changes in maternal weight. Further investigation is required to understand how phthalates may influence body composition and whether they contribute to the development of obesity and other cardiometabolic diseases in women. • Pregnancy is a critical life course event that influences metabolic health outcomes. • Phthalates are endocrine disrupting chemicals that may influence weight status. • Prenatal phthalate exposure was inversely associated with gestational weight gain. • Prenatal phthalate exposure was positively associated with long-term weight changes. [ABSTRACT FROM AUTHOR]

Associations between lead (Pb) and neurodevelopment have been studied widely in the context of global measures of cognitive function, such as IQ. Operant test batteries consist of behavioral tasks that can be used to target discrete cognitive and behavioral mechanisms, which contribute to global cognitive faculties. The goals of this study were to identify Pb-associated deficits in cognitive development and determine the underlying mechanisms involved, utilizing an operant test battery. We evaluated effect modification by child sex. This study utilized data from a prospective cohort in Mexico City. We included 549 participants aged 6-to-7 years with complete data on prenatal blood Pb measurements, Operant Test Battery (OTB) tasks, and demographic covariates. General linear models were used to examine the association of Pb levels at each prenatal timepoint and OTB performance. Effect modification by child sex was evaluated using 2-way interaction terms. In three of the operant tasks, we observed that higher late-pregnancy blood Pb concentrations were associated with greater response latencies. In the temporal processing task, we observed that higher late-pregnancy Pb exposure was associated with worse overall task performance. Further, in two operant tasks, the effects of Pb were dependent on the sex of the child, such that the effects of Pb were more pronounced in females in the condition position responding task, but stronger in males in the temporal processing task. Our results suggest that prenatal Pb concentrations yield broad dysregulation of executive functions, which can be attributed to dysregulation of temporal processing. In addition, we observed sex differences in two operant tasks suggesting that some Pb effects on neurocognitive function may be sexually dimorphic. • Operant testing procedures were used to attribute lead-associated deficits to discrete cognitive mechanisms • Higher prenatal lead (Pb) concentrations yield broad dysregulation of executive functions • Prenatal Pb concentrations dysregulations can be, in part, attributed to dysregulation of temporal processing • Sex differences were observed in two operant tasks suggesting that some Pb effectsmay be sexually dimorphic [ABSTRACT FROM AUTHOR]

• Phthalate mixture at pregnancy was associated with long-term insulin resistance. • Phthalate mixture at pregnancy was associated with long term adverse lipid profiles. • Associations with glycemia biomarkers were primarily driven by MECPTP and ∑DBP. • Associations with lipid biomarkers were primarily driven by MECPTP, ∑DBP, and MEP. • Pregnancy phthalates exposure may be associated with long-term metabolic health. Pregnancy induces numerous cardiovascular and metabolic changes. Alterations in these sensitive processes may precipitate long-term post-delivery health consequences. Studies have reported associations between phthalates and metabolic complications of pregnancy, but no study has investigated metabolic outcomes beyond pregnancy. To examine associations of exposure to phthalates during pregnancy with post-delivery metabolic health. We quantified 15 urinary phthalate biomarker concentrations during the second and third trimesters among 618 pregnant women from Mexico City. Maternal metabolic health biomarkers included fasting blood measures of glycemia [glucose, insulin, Homeostatic Model Assessment of Insulin Resistance [HOMA-IR], % hemoglobin A1c (HbA1c%)] and lipids (total, high-density lipoprotein (HDL), low-density lipoprotein (LDL) cholesterol, triglycerides), at 4–5 and 6–8 years post-delivery. To estimate the influence of the phthalates mixture, we used Bayesian weighted quantile sum regression and Bayesian kernel machine regression; for individual biomarkers, we used linear mixed models. As a mixture, higher urinary phthalate biomarker concentrations during pregnancy were associated with post-delivery concentrations of plasma glucose (interquartile range [IQR] difference: 0.13 SD, 95%CrI: 0.05, 0.20), plasma insulin (IQR difference: 0.06 SD, 95%CrI: −0.02, 0.14), HOMA-IR (IQR difference: 0.08 SD, 95% CrI: 0.01, 0.16), and HbA1c% (IQR difference: 0.15 SD, 95%CrI: 0.05, 0.24). Associations were primarily driven by mono-2-ethyl-5-carboxypentyl terephthalate (MECPTP) and the sum of dibutyl phthalate biomarkers (∑DBP). The phthalates mixture was associated with lower HDL (IQR difference: −0.08 SD, 95%CrI: −0.16, −0.01), driven by ∑DBP and monoethyl phthalate (MEP), and higher triglyceride levels (IQR difference: 0.15 SD, 95%CrI: 0.08, 0.22), driven by MECPTP and MEP. The overall mixture was not associated with total cholesterol and LDL. However, ∑DBP and MEP were associated with lower and higher total cholesterol, respectively, and MECPTP and ∑DBP were associated with lower LDL. Phthalate exposure during pregnancy is associated with adverse long-term changes in maternal metabolic health. A better understanding of timing of the exact biological changes and their implications on metabolic disease risk is needed. [ABSTRACT FROM AUTHOR]

Phthalate exposure has been associated with increased childhood behavioral problems. Existing studies failed to include phthalate replacements and did not account for high correlations among phthalates. Phthalates' exposure is higher in Mexico than in U.S. locations, making it an ideal target population for this study. To examine associations between 15 maternal prenatal phthalate metabolite concentrations and children's behavioral problems. We quantified phthalate metabolites in maternal urine samples from maternal-child dyads (n = 514) enrolled in the Programming Research in Obesity, Growth Environment and Social Stress (PROGRESS) birth cohort in Mexico City. We performed least absolute shrinkage and selection operator (LASSO) regressions to identify associations between specific-gravity adjusted log 2 -transformed phthalate metabolites and parent-reported 4–6 year old behavior on the Behavior Assessment System for Children (BASC-2), accounting for metabolite correlations. We adjusted for socio-demographic and birth-related factors, and examined associations stratified by sex. Higher prenatal mono-2-ethyl-5-carboxypentyl terephthalate (MECPTP) urinary concentrations were associated with increased hyperactivity scores in the overall sample (β = 0.57, 95% CI = 0.17, 1.13) and in girls (β = 0.54, 95% CI = 0.16, 1.08), overall behavioral problems in boys (β = 0.58, 95% CI = 0.20, 1.15), and depression scores in boys (β = 0.44, 95% CI = 0.06, 0.88). Higher prenatal monobenzyl phthalate (MBzP) concentrations were associated with reduced hyperactivity scores in girls (ß = −0.54, 95% CI = −1.08, −0.21). Our findings suggested that prenatal concentrations of phthalates and their replacements altered child neurodevelopment and those associations may be influenced sex. • Prenatal concentrations of phthalates and their novel replacements altered 4-6 year old child behavior. • Children exposed to higher prenatal MECPTP levels showed increased overall behavioral, depression, and hyperactivity scores. • Both magnitude and significance of the MECPTP-behavior associations differed by sex. • Girls born to mothers with higher prenatal MBzP concentrations were associated with reduced hyperactivity. [ABSTRACT FROM AUTHOR]

Prenatal phthalate exposures may affect processes that underlie offspring cardiometabolic health, but findings from studies examining these associations are conflicting. We examined associations between biomarkers of phthalate exposures during pregnancy with child lipid and adipokine levels. Data were from 463 mother-child pairs in the PROGRESS cohort of Mexico City. We quantified 15 phthalate metabolites in 2nd and 3rd trimester maternal urine samples and created an average pregnancy measure using the geometric mean. We evaluated the 15 metabolites as nine biomarkers, including four metabolite molar sums. We measured fasting serum triglycerides, non-HDL cholesterol, leptin, and adiponectin in children at the six-year follow-up visit (mean = 6.8 years). We estimated associations using linear regression, Bayesian kernel machine regression (BKMR), and weighted quantile sum (WQS) and assessed effect modification by sex. In BKMR and WQS models, higher concentrations of the total mixture of phthalate biomarkers were associated with lower triglycerides (β = −3.7% [-6.5, −0.78] per 1 unit increase in WQS biomarker index) and non-HDL cholesterol (β = −2.0 [-3.7, −0.25] ng/ml per increase in WQS biomarker index). Associations between individual biomarkers and child outcomes were largely null. We observed some evidence of effect modification by child sex for mono-3-carboxypropyl phthalate (β = 19.4% [1.26, 40.7] per doubling of phthalate) and monobenzyl phthalate (β = −7.6% [-14.4, -0.23]) in girls for adiponectin. Individual prenatal phthalate biomarkers were not associated with child lipid or adipokine levels. Contrary to our hypothesis, the total phthalate mixture was associated with lower child triglycerides and non-HDL cholesterol. • Total prenatal phthalates were associated with lower child triglycerides at age 6. • Total prenatal phthalates were associated with lower child non-HDL cholesterol. • Prenatal phthalate biomarkers were not associated with child adipokines. • Select sex-specific associations between phthalates and adiponectin were observed. [ABSTRACT FROM AUTHOR]