Search

Optimal nutrition during pregnancy is vital for both maternal and child health. Our objective was to explore if prenatal diet is associated with children’s height and body fat. Nutrient intake was assessed through a food-frequency questionnaire from 808 pregnant women and summarized to a nutrition index, “My Nutrition Index” (MNI). The association with children’s height and body fat (bioimpedance) was assessed with linear regression models. Secondary analysis was performed with BMI, trunk fat and skinfolds. Overall, higher MNI score was associated with greater height (β=0.47; (95% CI: 0.00, 0.94), among both sexes. Among boys, higher MNI was associated with 0.15 higher BMI z-scores, 0.12 body fat z-scores, 0.11 trunk fat z-scores, and larger triceps, and triceps + subscapular skinfolds (β=0.05 and β=0.06; on the log2 scale) (p-value

Summary Background Pregnancy is associated with deteriorations in maternal bone strength and heightened susceptibility to bone fractures. We aimed to investigate whether ambient particulate matter (PM)2·5 concentrations were associated with bone strength during pregnancy. Methods In this longitudinal cohort study, we analysed longitudinal data from women participating in the Programming Research in Obesity, Growth, Environment and Social Stressors (PROGRESS) cohort in Mexico City, Mexico. Eligible women were aged 18 years or older, at less than 20 weeks' gestation at the time of recruitment, planning to stay in Mexico City for the next 3 years, without heart or kidney disease, did not use steroids or anti-epileptic drugs, were not daily consumers of alcohol, and had access to a telephone. Daily ambient PM2·5 concentrations were estimated from a spatio-temporal model that was based on the individual's address. Trabecular bone strength was measured using quantitative ultrasound from the radius of the middle finger and cortical bone strength from the proximal phalanx of the middle finger, during the second trimester, third trimester, and 1 and 6 months post partum. Bone strength T scores were modelled with PM2·5 concentrations using linear mixed models and distributed lag models. Findings Adjusting for multiple exposure windows, each 10 ug/m3 increase in PM2·5 exposure concentrations in the first trimester was associated with a 0·18 SD decrease (95% CI −0·35 to −0·01; p=0·033) in ultrasound speed-of-sound (SOS) T score of trabecular bone strength from the second trimester until 6 months post partum. Similarly, each 10 μg/m3 increase in third trimester PM2·5 exposure was associated with a 0·18 SD decrease (–0·36 to −0·01; p=0·044) in the SOS T score of trabecular bone strength from the third trimester until 6 months post partum. PM2·5 exposure in the first month post partum was associated with a 0·20 SD decline (–0·39 to −0·01; p=0·043) in cortical bone strength until 6 months post partum. Interpretation Ambient PM2·5 exposure during and after pregnancy was associated with diminished trabecular and cortical bone strength. Early pregnancy PM2·5 exposure was associated with a greater decline in bone strength later during pregnancy. Late pregnancy and early post-partum exposures adversely affected the post-partum bone strength recovery. Technological and policy solutions to reduce PM2·5 pollution could improve public health by reducing bone fracture risk. Funding US National Institute of Environmental Health Sciences.

BACKGROUND: Working memory (WM) is critical for problem solving and reasoning. Beginning in infancy, children show WM capacity increasing with age but there are few validated tests of WM in very young children. Because rapid brain development may increase susceptibility to adverse impacts of prenatal neurotoxicant exposure, such as lead, tests of WM in very young children would help to delineate onset of developmental problems and windows of susceptibility. PURPOSE: Our objective was to assess the feasibility of administering a Delayed Spatial Alternation Task (DSAT) to measure WM among 18- and 24-month old children enrolled in an ongoing longitudinal birth cohort study and compare DSAT performance with age and general cognitive development. We further explored whether prenatal lead exposure impacted DSAT performance. METHODS: We assessed 457 mother-child pairs participating in the Programming Research in Obesity, GRowth, Environment and Social Stressors (PROGRESS) Study in Mexico City. The DSAT and Bayley Scales of Infant Development (BSID-III) were administered at 18- and 24-months. Lead was measured in maternal blood collected during pregnancy (MBPb) and in a subsample of children at 24-months (CBPb). We regressed DSAT measures on MBPb and CBPb, child sex, and maternal age, education, socioeconomic status, and household smoking. We compared DSAT performance to BSID-III performance with adjusted residuals. RESULTS: 24-month children perform better on the DSAT than 18-month children; 24-month subjects reached a higher level on the DSAT (3.3 (0.86) vs. 2.4 (0.97), p < 0.01), and had a higher number of correct responses (20.3 vs. 17.2, p < 0.01). In all DSAT parameters, females performed better than males. Maternal education predicted better DSAT performance; household smoking predicted worse DSAT performance. A higher number of correct responses was associated with higher BSID-III Cognitive scales at 18 months (r = 0.20, p < 0.01) and 24 months (r = 0.27, p < 0.01). MBPb and CPBb did not significantly predict DSAT performance. CONCLUSION: Improved performance on the DSAT with increasing age, the positive correlation with the BSID-III cognitive and language scales and the correlation with common sociodemographic predictors of neurodevelopment demonstrate the validity of the DSAT as a test of infant development.

Background We evaluated: 1) associations of prenatal manganese (Mn) levels with child neurodevelopment at 4 – 6 years; 2) effect modification by maternal anemia and iron deficiency; and 3) sex-specific effects. Methods We measured blood Mn, hemoglobin, and serum ferritin in mothers at the 2nd trimester, 3rd trimester, and at birth, and in cord blood from a prospective birth cohort in Mexico City (n=571). McCarthy Scales of Children’s Abilities were measured at 4 – 6 years. Using linear regression, we estimated associations between prenatal Mn and neurodevelopment, examined anemia and iron deficiency as effect modifiers, and analyzed associations by child sex. Results No direct associations were observed between Mn, anemia, or iron deficiency and McCarthy scales. Second trimester iron deficiency and 3rd trimester anemia modified the effect of Mn on child neurodevelopment. For instance, 2nd trimester Mn was positively associated child memory scores in mother’s with normal ferritin (1.85 (0.02, 3.45), but negatively associated in mother’s with low ferritin (−2.41 (−5.28, 0.47), interaction p value = 0.01), a pattern observed across scales. No effect modification at birth or in cord blood was observed. Conclusions Anemia/iron deficiency during pregnancy may modify Mn impacts on child neurodevelopment, particularly in boys.

Objective: To determine whether prenatal sex hormones from maternal saliva are associated with birth weight-for-gestational age. Study Design: We measured salivary progesterone, testosterone, estradiol, dehydroepiandrosterone (DHEA) and cortisone in 504 pregnant women in a Mexico City cohort in the. We performed linear and modified Poisson regression to examine associations of log-transformed hormones with birth weight-for-gestational age z-scores and the risk of small-for-gestational age (SGA) and large-for-gestational age (LGA) adjusting for maternal age, sex, BMI, parity, smoking, education and socioeconomic status. Results: 15% of infants were SGA and 2% were LGA. Each interquartile range increment in testosterone/estradiol ratio was associated with a 0.12 decrement in birth weight-for-gestational age z-score (95% CI: −0.27, −0.02) and a 50% higher risk of SGA versus appropriate-for-gestational age (AGA) (95% CI: 1.13, 1.99). Conclusion: Higher salivary testosterone/estradiol ratios may affect fetal growth, and identifying the predictors of hormone levels may be important to optimizing fetal growth.

Introduction: Lead (Pb) crosses the placenta and can cause oxidative stress, reduced fetal growth and neurological problems. The principal source of oxidative stress in human cells is mitochondria. Therefore, disruption of normal mitochondrial function during pregnancy may represent a primary mechanism behind the adverse effects of lead. We sought to assess the association of Pb exposure during pregnancy with mitochondrial DNA (mtDNA) content, a sensitive marker of mitochondrial function, in cord blood. Materials and methods: This study comprised mother-infant pairs from the Programming Research in Obesity, Growth, Environment and Social Stressors (PROGRESS) study, a prospective birth-cohort that enrolled 1050 pregnant women from Mexico City who were receiving prenatal care between December 2007 and July 2011. Quantitative PCR was used to calculate relative MtDNA content (mitochondrial-to-nuclear DNA ratio (mtDNA/nDNA)) in cord blood. Lead concentrations in both maternal blood (2nd and 3rd trimester and at delivery day) and in cord blood were measured by ICP-MS. Multivariable regression models adjusting for multiple confounders were fitted with 410 mother-infant pairs for whom complete data for mtDNA content, lead levels, and covariates were available. Results: Maternal blood Pb measured in the second (mean 3.79 μg/dL, SD 2.63; β = 0.059, 95% CI 0.008, 0.111) and third trimester (mean 3.90 μg/dL; SD 2.84; β = 0.054, 95% CI 0.002, 0.107) during pregnancy and PB in cord blood (mean 3.50 μg/dL, SD 2.59; β = 0.050, 95% CI 0.004; 0.096) were associated with increased cord blood mtDNA content (mean 1.46, SD 0.44). In two-way interaction analyses, cord blood Pb marginally interacted with gestational age leading to an increase in mtDNA content for pre-term births (Benjamini-Hochberg False Discovery Rate correction; BH-FDR = 0.08). Conclusion: This study shows that lead exposure in pregnancy alters mtDNA content in cord blood; therefore, alteration of mtDNA content might be a mechanism underlying the toxicity of lead. Keywords: mtDNA content, Lead exposure, Pregnancy, Mitochondrial dysfunction, Cord blood

BACKGROUND: Trace metal concentrations may affect cardio-metabolic risk, but the role of prenatal exposure is unclear. We examined: 1) the relationship between blood metal concentrations during pregnancy and child cardio-metabolic risk factors; 2) overall effects of metals mixture (essential vs. nonessential); and 3) interactions between metals. METHODS: We measured 11 metals in maternal 2(nd) trimester whole blood in a prospective birth cohort in Mexico City. In children 4–6 years old, we measured body mass index (BMI), percent body fat, and blood pressure (N=609); and plasma hemoglobin A1C (HbA1c) , non-high density lipoprotein (HDL) cholesterol, triglycerides, leptin, and adiponectin (N=411). We constructed cardio-metabolic component scores using age- and sex-adjusted z-scores and averaged five scores to create a global risk score. We estimated linear associations of each metal with individual z-scores and used Bayesian Kernel Machine Regression to assess metal mixtures and interactions. RESULTS: Higher total metals were associated with lower HbA1c, leptin, and systolic blood pressure, and with higher adiponectin and non-HDL cholesterol. We observed no interactions between metals. Higher selenium was associated with lower triglycerides in linear (β=−1.01 z-score units per 1 unit ln(Se), 95%CI = −1.84; −0.18) and Bayesian Kernel Machine Regression models. Manganese was associated with decreased HbA1c in linear models (β = −0.32 and 95% CI: −0.61, −0.03). Antimony and arsenic were associated with lower leptin in Bayesian Kernel Machine Regression models. Essential metals were more strongly associated with cardio-metabolic risk than were nonessential metals. CONCLUSIONS: Low essential metals during pregnancy were associated with increased cardio-metabolic risk factors in childhood.

Reward motivation is a complex umbrella term encompassing the cognitions, emotions, and behaviors involved in the activation, execution, and persistence of goal-directed behavior. Altered reward motivation in children is characteristic of many neurodevelopmental and psychiatric disorders. Previously difficult to operationalize, the Progressive Ratio (PR) task has been widely used to assess reward motivation in animal and human studies, including children. Because the neural circuitry supporting reward motivation starts developing during pregnancy, and is sensitive to disruption by environmental toxicants, including metals, the goal of this study was to examine the association between prenatal concentrations of a mixture of neurotoxic metals and reward motivation in children. We measured reward motivation by administering a PR test to 373 children ages 6–8 years enrolled in the Programming Research in Obesity, Growth, Environment and Social Stressors (PROGRESS) Study in Mexico City. Children were asked to press a response lever for a token reward; one press on the response lever was required to earn the first token and each subsequent token required an additional 10 lever presses. Maternal blood concentrations of lead, manganese, zinc, arsenic, cadmium, and selenium were measured using inductively-coupled plasma mass spectrometry during the 2(nd) and 3(rd) trimesters of pregnancy. We performed generalized Weighted Quantile Sum (gWQS) regression analyses to examine associations between the prenatal metal mixture and reward motivation; adjusting for child sex, birthweight and age; and maternal IQ, education, and socioeconomic status. The prenatal metal mixture was significantly associated with higher motivation as indicated by more lever presses (β = 0.02, p < 0.001) and a shorter time between receiving the reinforcer and the first press (β = 0.23, p = 0.01), and between subsequent presses (β = 0.07, p = 0.005). Contributions of different metals to this association differed by trimester and child sex. These findings suggest that children with increased exposure to metal during the 2(nd) and 3(rd) trimesters of gestation demonstrate increased reward motivation, which may reflect a tendency to perseverate or hypersensitivity to positive reinforcement.

Exposure to endocrine disrupting chemicals (EDCs) may impact early growth, although information is limited on exposure to combination of multiple EDCs. We aimed to evaluate the effect of prenatal exposure to EDC mixtures on birthweight z-scores and childhood weight trajectories. Twenty-six proven and suspected EDCs, were analyzed in prenatal urine and blood samples from 1118 mothers participating in the Swedish Environmental Longitudinal Mother and child Asthma and allergy (SELMA) study. Two growth parameters were estimated from each child’s weight trajectory from birth to 5.5 years of age: infant growth spurt rate and age at infant peak growth velocity (PGV). Weighted quantile sum (WQS) regression was used to estimate the mixture effect and identify chemicals of concern. A one-unit increase in the EDC mixture WQS index, was associated with decreased birthweight z-scores of 0.11 (95% CI − 0.16, − 0.06), slower infant growth spurt rate of 0.01 (95% CI − 0.03, − 0.01, on the log10 scale), and delayed age at infant PGV of 0.15 months (95% CI 0.07, 0.24) after adjusting for potential confounders. Stratified analysis by sex, showed that delayed age at infant PGV was mostly observed in girls with 0.51 months (95% CI 0.26, 0.76). Identified chemicals of concern included perfluorinated alkyl substances (PFAS), Triclosan, phthalates, non-phthalate plasticizers, bisphenols, polycyclic aromatic hydrocarbons, pesticides and PCBs. Prenatal exposure to EDC mixtures was associated with lower birthweight and altered infant weight gain trajectories.

Aims: The authors sought to examine associations between urinary exosomal miRNAs (exo-miRs), emerging biomarkers of renal health, and cardiorenal outcomes in early childhood. Materials & methods: The authors extracted exo-miRs in urine from 88 healthy Mexican children aged 4–6 years. The authors measured associations between 193 exo-miRs and cardiorenal outcomes: systolic/diastolic blood pressure, estimated glomerular filtration rate and urinary sodium and potassium levels. The authors adjusted for age, sex, BMI, socioeconomic status, indoor tobacco smoke exposure and urine specific gravity. Results: Multiple exo-miRs were identified meeting a false discovery rate threshold of q

Background Sedentary behavior is a worldwide public health concern. There is consistent and growing evidence linking sedentary behavior to mortality and morbidity. Early monitoring and assessment of environmental factors associated with sedentary behaviors at a young age are important initial steps for understanding children's sedentary time and identifying pertinent interventions. Objective This study examines the association between daily temperature (maximum, mean, minimum, and diurnal variation) and all-day sedentary time among 4-6 year old children in Mexico City (n = 559) from the year 2013 to 2015. Methods We developed a spatiotemporally resolved hybrid satellite-based land use regression temperature model and calculated percent daily sedentary time from aggregating 10-second epoch vertical counts captured by accelerometers that participants wore for one week. We modeled generalized additive models (GAMs), one for each temperature type as a covariate (maximum, mean, minimum, and diurnal variation). All GAMs included percent all-day sedentary time as the outcome and participant-level random intercepts to account for repeated measures of sedentary time. Our models were adjusted for demographic factors and environmental exposures. Results Daily maximum temperature, mean temperature, and diurnal variation have significant negative linear relationships with all-day sedentary time (p

Environmental exposures to a myriad of chemicals are associated with adverse health effects in humans, while good nutrition is associated with improved health. Single chemical in vivo and in vitro studies demonstrate causal links between the chemicals and outcomes, but such studies do not represent human exposure to environmental mixtures. One way of summarizing the effect of the joint action of chemical mixtures is through an empirically weighted index using weighted quantile sum (WQS) regression. My Nutrition Index (MNI) is a metric of overall dietary nutrition based on guideline values, including for pregnant women. Our objective is to demonstrate the use of an index as a metric for more causally linking human exposure to health outcomes using observational data. We use both a WQS index of 26 endocrine-disrupting chemicals (EDCs) and MNI using data from the SELMA pregnancy cohort to conduct causal inference using g-computation with counterfactuals for assumed either reduced prenatal EDC exposures or improved prenatal nutrition. Reducing the EDC exposure using the WQS index as a metric or improving dietary nutrition using MNI as a metric, the counterfactuals in a causal inference with one SD change indicate significant improvement in cognitive function. Evaluation of such a strategy may support decision makers for risk management of EDCs and individual choices for improving dietary nutrition.

Study objectives Maternal antenatal stress may influence offspring development and behavior, but any association with child sleep is unknown. Methods From 2007 to 2011, we recruited pregnant women in Mexico City to the Programming Research in Obesity, Growth, Environment, and Social Stressors prebirth cohort. Mothers completed the Perceived Stress Scale (PSS, a 4-item questionnaire assessing past-month stress) and the Crisis in Family Systems measure assessing negative life events (NLEs; how many domains among the 11 assessed in which the mother experienced a stressful event in the prior 6 months)—with higher scores reflecting higher stress—and provided 5 timed salivary samples per day on 2 consecutive days, from which we derived cortisol area under the curve, slope, and awakening response. At age 4-6 years, children's sleep was estimated using accelerometry over a 7-day period. We performed secondary analysis of associations of antenatal maternal stress with child sleep duration and efficiency (time asleep/time in bed) using linear regression adjusted for maternal and child characteristics. Results Among 594 mother-child dyads, mean antenatal PSS score was 5.2 (SD = 3.2) out of 16, and mean NLE was 3.2 (SD = 2) out of 11; child sleep duration was 7.7 hours (SD = 0.7), and sleep efficiency was 79% (SD = 6). There was no association between any of the stress measures—PSS, NLE, or salivary cortisol—and sleep duration or sleep efficiency in adjusted or unadjusted models. Conclusions Among mother-child dyads in a Mexico City cohort, antenatal stress was not associated with important changes in child sleep at 4-6 years.

Background: As population lead levels decrease, the toxic effects of lead may be distributed to more sensitive populations, such as infants with poor fetal growth. Objectives: To determine the association of prenatal lead exposure and fetal growth; and to evaluate whether infants with poor fetal growth are more susceptible to lead toxicity than those with normal fetal growth. Methods: We examined the association of second trimester maternal blood lead levels (BLL) with birthweight-for-gestational age (BWGA) z-score in 944 mother-infant participants of the PROGRESS cohort. We determined the association between maternal BLL and BWGA z-score by using both linear and quantile regression. We estimated odds ratios for small-for-gestational age (SGA) infants between maternal BLL quartiles using logistic regression. Maternal age, body mass index, socioeconomic status, parity, household smoking exposure, hemoglobin levels, and infant sex were included as confounders. Results: While linear regression showed a negative association between maternal BLL and BWGA z-score (β = −0.06 z-score units per log2 BLL increase; 95% CI: −0.13, 0.003; P = 0.06), quantile regression revealed larger magnitudes of this association in the

Lead exposure during pregnancy remains a public health problem with potential lifelong impacts on children's growth and development. Mexico is unique in that stunting and obesity are both major public health concerns in children. This situation might be exacerbated by lead exposure which remains more common in Mexico than in the United States due in part to the use of lead glazed pottery in food preparation and storage. Our objective is to determine how lead exposure during pregnancy is associated with children's growth parameters, including height, weight, body mass index and percentage body fat measured between ages 4-6 years old in a Mexico City pregnancy cohort. Blood lead was collected in the 2nd and 3rd trimester of pregnancy as well as at delivery. Bone lead was assessed in mothers as a long term exposure biomarker. We performed multivariable linear regression analyses to assess the association between each of these lead exposure biomarkers and child anthropometry. We found a significant negative association between maternal 3rd trimester blood lead concentration and offspring height for age (β-0.10; 95% CI -0.19, -0.01), and a negative association between maternal 3rd trimester blood lead concentration and weight for age (β-0.11; 95% CI -0.22,-0.003). Our results in this Mexican population add to previous findings of an association of lead and decreased stature and weight in early childhood. Ongoing follow-up and longitudinal analyses may help elucidate how this impacts growth trajectory and other children's health outcomes.

Aim: Bacterial vaginosis may lead to preterm birth through epigenetic programming of the inflammatory response, specifically via miRNA expression. Methods: We quantified bacterial 16S rRNA, cytokine mRNA and 800 miRNA from cervical swabs obtained from 80 women at 16–19 weeks’ gestation. We generated bacterial and cytokine indices using weighted quantile sum regression and examined associations with miRNA and gestational age at delivery. Results & discussion: Each decile of the bacterial and cytokine indices was associated with shorter gestations (p < 0.005). The bacterial index was associated with miR-494, 371a, 4286, 185, 320e, 888 and 23a (p < 0.05). miR-494 remained significant after false discovery rate correction (q < 0.1). The cytokine index was associated with 27 miRNAs (p < 0.05; q < 0.01). Conclusion: Future investigation into the role of bacterial vaginosis- and inflammation-associated miRNA and preterm birth is warranted.

Infants born prematurely or with low birth weights are more susceptible to kidney dysfunction throughout their lives. Multiple proteins measured in urine are noninvasive biomarkers of subclinical kidney damage, but few studies have examined the joint effects of multiple biomarkers. We conducted an exploratory study of 103 children in the Programing Research in Obesity, Growth, Environment, and Social Stressors (PROGRESS) longitudinal birth cohort, and measured nine proteins selected a priori in banked spot urine samples collected at ages 4-6. The goal of our study was to explore the combined effects of kidney damage biomarkers previously associated with birth outcomes. To do this, we generated kidney biomarker indices using weighted quantile sum regression and assessed associations with length of gestation or birth weight. A decile increase in each kidney biomarker index was associated with 2-day shorter gestations (β = -2.0, 95% CI: -3.2, -0.9) and 59-gram lower birth weights (β = -58.5, 95% CI: -98.3, -18.7), respectively. Weights highlighting the contributions showed neutrophil gelatinase-associated lipocalin (NGAL) (60%) and osteopontin (19%) contributed most to the index derived for gestational age. NGAL (66%) and beta-2-microglobulin (10%) contributed most to the index derived for birth weight. Joint analyses of multiple kidney biomarkers can provide integrated measures of kidney dysfunction and improved statistical assessments compared to biomarkers assessed individually. Additionally, shorter gestations and lower birth weights may contribute to subclinical kidney damage measurable in childhood.

We examined the independent associations of moderate to vigorous physical activity (MVPA) and sedentary time (ST) with cardiometabolic indicators in Mexican children (4-6 years of age). We conducted a cross-sectional study (n = 400) using the measures of MVPA and ST (7-day accelerometry) and the following indicators: % body fat, waist circumference, body mass index (BMI) z-score, glycated haemoglobin, blood glucose, triglycerides, total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, leptin, adiponectin and resting blood pressure. We examined the independent associations of MVPA and ST with cardiometabolic indicators through confounder-adjusted and mutually adjusted (including both MVPA and ST) linear regression models. Confounder-adjusted models showed that MVPA was associated with higher BMI z-scores and lower adiponectin levels in girls and lower body fat among boys. ST was associated with higher body fat, in the full sample, and lower LDL cholesterol among boys. After mutually adjusting for MVPA and ST, MVPA (10-minute increase) remained significantly associated with BMI z-score in girls (β = 0.187, 95% CI: 0.019, 0.356) and ST (60-minute increase) remained significantly associated with higher body fat (β = 1.11%, 95% CI: 0.019, 2.203) among boys and higher glycated haemoglobin (β = 0.047% points, 95% CI: 0.000, 0.094) in the full sample. In preschool-aged children, the objective measures of ST and MVPA were associated with small differences in cardiometabolic health indicators. ST was unfavourably associated with some cardiometabolic indicators even after adjusting for MVPA, and thus appeared to have a more significant role than MVPA, especially in boys. Future longitudinal studies should confirm these results.

Background Occupational studies have shown an association between elevated Mn exposure and depressive symptoms. Blood Mn (BMn) naturally rises during pregnancy due to mobilization from tissues, suggesting it could contribute to pregnancy and postpartum depressive symptoms. Objectives To assess the association between BMn levels during pregnancy and postpartum depression (PPD), creating opportunities for possible future interventions. Methods We studied 561 women from the reproductive longitudinal Programming Research in Obesity, Growth, Environment, and Social Stressors (PROGRESS) cohort in Mexico City. BMn was measured at the 2nd and 3rd trimesters, as well as delivery. The Edinburgh Postnatal Depression Scale (EPDS) was used to assess PPD symptoms at 12-months postpartum. We used a generalized linear model assuming a Poisson distribution to assess the association between BMn levels and PPD, with adjustments for age, stress and depressive symptoms during pregnancy, education, socioeconomic status, and contemporaneous blood lead levels. Results The mean ± standard deviation (SD) EPDS score at 12-months postpartum was 6.51 ± 5.65, and 17.11% of women met the criteria for possible PPD (score ≥ 13). In adjusted models, BMn during the 3rd trimester (β: 0.13, 95% CI: 0.04-0.21) and BMn levels averaged at the 2nd and 3rd trimester (β: 0.14, 95% CI: 0.02-0.26) had a positive association with EPDS scores at 12 months postpartum. BMn at the 2nd trimester (β: 0.07, 95% CI: -0.09-0.22) and delivery (β: 0.03, 95% CI: -0.04-0.10) had a non-significant positive association with EPDS scores at 12-months postpartum. Stress and depressive symptoms during pregnancy was associated with higher EPDS scores at 12-months postpartum in all of the adjusted models but were only significant when either BMn during 3rd trimester or BMn averaged across 2nd and 3rd trimester was assessed as the exposure. Discussion Our results demonstrate that elevated BMn levels during pregnancy predict PPD symptoms and could be a potential pathway for intervention and prevention of PPD.

BACKGROUND: Exposure to air pollution is associated with increased blood pressure (BP) in adults and children. Some evidence suggests that air pollution exposure during the prenatal period may contribute to adverse cardiorenal health later in life. Here we apply a distributed lag model (DLM) approach to identify critical windows that may underlie the association between prenatal particulate matter ≤ 2.5 μm in diameter (PM(2.5)) exposure and children’s BP at ages 4 to 6 years. METHODS: Participants included 537 mother-child dyads enrolled in the Programming Research in Obesity, GRowth Environment, and Social Stress (PROGRESS) longitudinal birth cohort study based in Mexico City. Prenatal daily PM(2.5) exposure was estimated using a validated satellite-based spatio-temporal model and BP was measured using the automated Spacelabs system with a sized cuff. We used distributed lag models (DLMs) to examine associations between daily PM(2.5) exposure and systolic and diastolic BP (SBP and DBP), adjusting for child’s age, sex and BMI, as well as maternal education, preeclampsia and indoor smoking report during the second and third trimester, seasonality and average postnatal year 1 PM(2.5) exposure. RESULTS: We found that PM(2.5) exposure between weeks 11 to 32 of gestation (days 80 to 226) was significantly associated with children’s increased SBP. Similarly, PM(2.5) exposure between weeks 9 to 25 of gestation (days 63 to 176) was significantly associated with increased DBP. To place this into context, a constant 10 μg/m(3) increase in PM(2.5) sustained throughout this critical window would predict a cumulative increase of 2.6 mmHg (CI: 0.5, 4.6) in SBP and 0.88 mmHg (CI: 0.1, 1.6) in DBP at ages 4 to 6 years. In a stratified analysis by sex, this association persisted in boys but not in girls. CONCLUSIONS: Second and third trimester PM(2.5) exposure may increase children’s BP in early life. Further work investigating PM(2.5) exposure with BP trajectories later in childhood will be important to understanding cardiorenal trajectories that may predict adult disease. Our results underscore the importance of reducing air pollution exposure among susceptible populations, including pregnant women.

Introduction: Manganese (Mn) is an essential nutrient but also a toxicant at high exposures, when it can induce oxidative stress (OS). Mn uptake is inversely correlated with iron status, therefore anemic individuals may be more susceptible to Mn overload induced-OS, which can manifest as changes in mitochondrial DNA copy number (mtDNA CN). Our objectives were to: 1) determine stage-specific associations of prenatal Mn exposure with cord blood MtDNA CN; and 2) investigate effect modification by maternal anemia, ferritin, and mean corpuscular volume (MCV). Materials and methods: We measured whole blood Mn, hemoglobin, serum ferritin, and MCV in the 2nd and 3rd trimester, in maternal blood at birth, and in cord blood from a prospective birth cohort in Mexico City, Mexico (n = 485). We then extracted DNA from cord blood leukocytes to determine mtDNA CN. We used robust regression to measure associations between Mn and mtDNA CN at each trimester and at birth. Anemia (hemoglobin ≤11 g/dL), iron deficiency (ferritin ≤15 ng/mL) and MCV (stratified at median), were examined as effect modifiers. Results: Mn levels increased throughout pregnancy, and Mn was inversely correlated with ferritin. We observed a positive association between Mn in the 3rd trimester and Mn in cord blood and mtDNA CN (β = 0.04–0.05; 95% CI = 0.01, 0.08). Anemia significantly modified the association between mtDNA CN and Mn in the 2nd trimester. We found a positive association between 2nd trimester Mn and mtDNA CN in mothers with normal hemoglobin, and a negative association in those with low hemoglobin. (βhigh = 0.06; 95% CI = 0.01, 0.11; p = 0.01 and βlow = −0.06; 95% CI = 0.03, −0.13; p = 0.06). No associations were detected between anemia, iron deficiency and MCV and mtDNA CN. Conclusions: Maternal blood Mn in the 3rd trimester and in cord blood was positively associated with mtDNA CN, suggesting that higher late pregnancy prenatal Mn exposures can impact newborn mitochondria by promoting OS. Furthermore, 2nd trimester Mn was positively associated with mtDNA in non-anemic mother-child pairs but inversely associated in anemic individuals, indicating potential interactions between Mn and chronic anemia. Keywords: Prenatal exposure, Manganese, Anemia, Iron deficiency, Mitochondria, Mitochondrial DNA

Background/Aim: Global increases in sedentary behavior are a major public health concern requiring research into its causes. We investigate environmental factors such as temperature and green space...

Background: Adequate levels of beneficial nutrients are important for neurodevelopment. Although, nutrients are ingested in combination, considering nutrients as a mixture has not been studied with...

Background: The programming of sleep architecture begins in pregnancy and depends upon optimal in utero formation and maturation of the neural connectivity of the brain. Particulate air pollution exposure can disrupt fetal brain development but associations between fine particulate matter (PM2.5) exposure during pregnancy and child sleep outcomes have not been previously explored. Methods: Analyses included 397 mother-child pairs enrolled in a pregnancy cohort in Mexico City. Daily ambient prenatal PM2.5 exposure was estimated using a validated satellite-based spatio-temporally resolved prediction model. Child sleep periods were estimated objectively using wrist-worn, continuous actigraphy over a 1-week period at age 4–5 years. Data-driven advanced statistical methods (distributed lag models (DLMs)) were employed to identify sensitive windows whereby PM2.5 exposure during gestation was significantly associated with changes in sleep duration or efficiency. Models were adjusted for maternal education, season, child's age, sex, and BMI z-score. Results: Mother's average age was 27.7 years, with 59% having at least a high school education. Children slept an average of 7.7 h at night, with mean 80.1% efficiency. The adjusted DLM identified windows of PM2.5 exposure between 31 and 35 weeks gestation that were significantly associated with decreased sleep duration in children. In addition, increased PM2.5 during weeks 1–8 was associated with decreased sleep efficiency. In other exposure windows (weeks 39–40), PM2.5 was associated with increased sleep duration. Conclusion: Prenatal PM2.5 exposure is associated with altered sleep in preschool-aged children in Mexico City. Pollutant exposure during sensitive windows of pregnancy may have critical influence upon sleep programming. Keywords: Particulate matter, Air pollution, Prenatal, Sleep, Child, Preschool-aged

Adequate nutrition is important for neurodevelopment. Although nutrients are ingested in combination, the impact of specific nutrients within the context of a nutrient mixture has not been studied with respect to health, such as neurodevelopment. Therefore, we examined the impact of prenatal and childhood nutrient mixtures on neurodevelopmental outcomes. Participants included mother–child pairs in the Programming Research in Obesity, Growth, Environment, and Social Stress (PROGRESS) prospective birth cohort in Mexico City. We assessed prenatal and child micro- and macronutrient profiles among 65 and 329 children, respectively, via food frequency questionnaires. Neurodevelopmental outcomes of 4–6 year-old children were measured using the McCarthy Scales of Children’s Abilities (MSCA). We conducted weighted quantile sum (WQS) regression analyses to calculate indices reflecting “good” and “poor” prenatal and childhood nutrition. After adjusting for maternal education, socioeconomic status, the Home Observation for Measurement of the Environment (HOME) score, and total caloric intake, the good prenatal and childhood nutrition indices predicted more favorable neurodevelopment, while both poor nutrition indices predicted poorer neurodevelopment. These associations were stronger in prenatal than childhood models. Monounsaturated fats predicted various neurodevelopmental abilities relatively strongly in both models. Prenatal and childhood consumption of combinations of beneficial nutrients may contribute to more favorable neurodevelopment.

Background Phthalates are known endocrine disruptors and peroxisome proliferator-activated receptor (PPAR) activators, potentially capable of promoting an obesogenic effect. Pregnant women are especially vulnerable to phthalate exposure due to physiological and metabolic changes during pregnancy, including those related to the metabolism of xenobiotics. Phthalate exposure during pregnancy has been associated with early gestational weight gain, however, its effect on long-term weight gain remains unclear. The aim of the present study was to evaluate the association between phthalate exposure during pregnancy and long-term changes in weight among women. Methods Urinary phthalate concentrations, socioeconomic, anthropometry and information on diet and socioeconomic status were collected during pregnancy from 178 women from the Early Life Exposure in Mexico to Environmental Toxicants (ELEMENT) birth cohort. Maternal body weight and diet information was also collected up to 5 times in the first year postpartum and twice during follow-up visits 5.2–10.7 years later. A path analysis was performed to assess associations between urinary phthalate metabolite levels during pregnancy and change in weight (kg) per year after delivery, including age, education, living with/without partner, parity, daily energy intake and breastfeeding duration. Results The mean age at pregnancy was 27.3 ± 5.9 years and mean body mass index during the first postpartum year was 27.07 ± 4.22 kg/m2. On average, women gained 3.48 kg (0.52 ± 0.84 kg/year). A unit increase in log-transformed mono-3-carboxypropyl phthalate (MCPP) was associated with 0.33 kg (95% CI: 0.09, 0.56) higher weight gain per year, and mono-benzyl phthalate (MBzP) with 0.21 kg (95% CI: −0.38, −0.03) lower weight gain per year. Conclusion Exposure to certain phthalates during pregnancy may be associated with long-term weight change in women. More studies on the effects of phthalate exposure during pregnancy on women's long-term health are required.

Objective Prepregnancy weight may not always be known to women. A model was developed to estimate prepregnancy weight from measured pregnancy weight. Methods The model was developed and validated using participants from two studies (Project Viva, n = 301, model development; and Fit for Delivery [FFD], n = 401, model validation). Data from the third study (Programming Research in Obesity, Growth, Environment and Social Stressors [PROGRESS]), which included women from Mexico City, were used to demonstrate the utility of the newly developed model to objectively quantify prepregnancy weight. Results The model developed from the Project Viva study validated well with low bias (R2 = 0.95; y = 1.02x - 0.69; bias = 0.68 kg; 95% CI: -4.86 to 6.21). Predictions in women from FFD demonstrated good agreement (R2 = 0.96; y = 0.96x + 4.35; bias = 1.60 kg; 95% CI: -4.40 to 7.54; error range = -11.25 kg to 14.73 kg). High deviations from model predictions were observed in the Programming Research in PROGRESS (R2 = 0.81; y = 0.89x + 9.61; bias = 2.83 kg; 95% CI: -7.70 to 12.31; error range = -39.17 kg to 25.73 kg). The model was programmed into software (https://www.pbrc.edu/research-and-faculty/calculators/prepregnancy/). Conclusions The developed model provides an alternative to determine prepregnancy weight in populations receiving routine health care that may not have accurate knowledge of prepregnancy weight. The software can identify misreporting and classification into incorrect gestational weight gain categories.

Background: High blood pressure (BP) in childhood is frequently renal in origin and a risk factor for adult hypertension and cardiovascular disease. Shorter gestations are a known risk factor for increased BP in adults and children, due in part to a nephron deficit in children born preterm. As nephrogenesis is incomplete until 36 weeks gestation, prenatal lead exposure occurring during a susceptible period of renal development may contribute to programming for later life renal disease. The relationship between shorter gestation and children's BP has not yet been explored to identify i) critical windows using nonlinear piecewise models or ii) combined with other early life risk factors such as prenatal lead exposure. Objectives: (1) To evaluate the nonlinear relationship between lower gestational age and childhood BP measured at 4–6 years of age, and (2) to investigate modification by prenatal lead exposure. Methods: In a prospective longitudinal birth cohort, we assessed 565 children between 4 and 6 years of age (mean: 4.8 years) in the PROGRESS cohort in Mexico City, Mexico. Gestational age at delivery was calculated using maternal report of last menstrual period (LMP) and confirmed with Capurro physical examination at birth. We measured pregnant women's blood lead levels (BLLs) in the second trimester via inductively coupled plasma-mass spectrometry and children's BP using an automated device. We performed both linear and nonlinear piecewise regression analyses to examine associations of gestational age with children's BP adjusting for children's age, sex, height, prenatal exposure to smoke, and maternal socioeconomic status. We stratified to assess modification by prenatal lead exposure, and used a data-adaptive approach to identify a lead cutpoint. Results: Maternal second trimester BLLs ranged from 0.7 to 17.8 μg/dL with 112 (20%) women above the CDC guideline level of 5 μg/dL. In adjusted linear regression models, a one week reduction in gestational age was associated with a 0.5 mm Hg (95%CI: 0.2, 0.8) increase in SBP and a 0.4 mm Hg (95%CI 0.1, 0.6) increase in DBP. Our nonlinear models suggested evidence for different magnitude estimates on either side of an estimated join-point at 35.9 weeks' gestation, but did not reach statistical significance. However, when stratified by prenatal lead exposure, we identified a cutpoint lead level of concern of 2.5 μg/dL that suggested an interaction between gestational age and blood lead. Specifically, for BLLs ≥ 2.5 μg/dL, SBP was 1.6 (95%CI: 0.3, 2.9) mm Hg higher per each week reduction in gestational age among children born before 37.0 weeks; and among children born after 37.0 weeks, this relationship was attenuated yet remained significant [β: 0.9, 95%CI (0.2, 1.6)]. At BLLs below 2.5 μg/dL, there was no appreciable association between lower gestational age and SBP. Conclusions: Our findings suggest that shorter gestation combined with higher prenatal lead exposure contributes to a higher risk of increased SBP at 4–6 years of age, particularly among infants born

Background: Metal exposure alters neurodevelopmental outcomes; little is known about critical windows of susceptibility when exposure exerts the strongest effect. Objective: To examine associations between dentine biomarkers of manganese (Mn), zinc (Zn) and lead (Pb) and later childhood behaviors. Methods: Subjects enrolled in a longitudinal birth cohort study in Mexico City provided naturally shed deciduous teeth. We estimated weekly prenatal and postnatal dentine Mn, Zn and Pb concentrations in teeth using laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) and measured behavior at ages 8–11 years of age using the Behavior Assessment System for Children, 2nd edition (BASC-2). We used distributed lag models and lagged weighted quantile sum regression to identify the role of individual and combined dentine biomarkers of Mn, Zn and Pb on behavioral outcomes controlling for maternal education and gestational age. Results: Among the 133 subjects included in this study, prenatal and early postnatal dentine Mn appeared protective against childhood behavioral problems, specifically hyperactivity and attention. Postnatal dentine Mn was associated with increased reporting of internalizing problems, specifically anxiety. At 6 months, a 1-unit increase (unit = 1 SD of log concentration) in Mn was associated with a 0.18-unit (unit = 1 SD of BASC-2 score) increase in internalizing symptoms score and a 0.25-unit increase in anxiety. Postnatal Pb was associated with increasing anxiety symptoms; at 12 months, a 1-unit increase in Pb was associated with a 0.4 unit increase in anxiety symptoms. When examined as a metal mixture, we observed two potential windows of susceptibility to increased anxiety symptoms: the first window (0–8 months) appeared driven by Mn, the second window (8–12 months) was driven by the metal mixture and dominated by Pb. A 1-unit increase in the mixture index was associated with a 0.7-unit increase in SD of anxiety symptoms. Conclusions: Childhood behaviors may demonstrate postnatal windows of susceptibility to individual and mixed metal concentrations measured in deciduous teeth. Prenatal dentine Mn may be protective, while excessive early postnatal Mn may increase risk for adverse behaviors. In combination, higher concentrations of Mn, Zn and Pb may have an adverse impact on behavior. Keywords: Dentine biomarkers, Child behavior, Metal mixtures, Anxiety, Manganese

CONTEXT: Early life cortisol plays an important role in bone, muscle, and fat mobilization processes, which could influence body composition, affecting anthropometric indicators such as weight and height. OBJECTIVE: To explore the association between diurnal cortisol levels and growth indexes in children from 12 to 48 months of age. DESIGN: This study includes data from 404 children from the Programming Research in Obesity, Growth, Environment and Social Stressors Mexican birth cohort. Cortisol was measured in eight saliva samples collected at four time points during the day (from wakeup to bedtime), over 2 days, when the child was either 12, 18, or 24 months old. Total daytime cortisol levels were calculated by averaging the area under the curve (AUC) for the 2 days. Height and weight were measured from 12 to 48 months of age. Growth indexes were constructed according to z scores following World Health Organization standards: weight-for-age z score (Z-WFA), height/length-for-age z score, weight-for-height/length z score (Z-WFH), and body mass index–for-age z score (Z-BMIFA). Mixed models were used to analyze the association between cortisol AUC quartiles and growth indexes. RESULTS: Cortisol showed an inverted U-shaped association with the four growth indexes. Compared with the first quartile, all quartiles had a positive association with indexes that include weight, with the second quartile having the strongest association, resulting in an average change of β (95% CI) 0.38 (0.13–0.64) for Z-WFA, 0.36 (0.10–0.62) for Z-WFH, and 0.43 (0.17–0.69) for Z-BMIFA. CONCLUSIONS: Results suggest that early life daytime cortisol levels, as a reflection of hypothalamic-pituitary-adrenal axis development, might influence growth in early infancy.