Ixel Hernandez-Castro
Postdoctoral Scholar, Epidemiology
Honors & Awards
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Propel Postdoctoral Scholar, Stanford University School of Medicine (August 2023)
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Gates Millenium Scholar, Bill and Melinda Gates Foundation (May 2014)
All Publications
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Maternal Urinary Fluoride and Child Neurobehavior at Age 36 Months.
JAMA network open
2024; 7 (5): e2411987
Abstract
Recent studies in Canadian and Mexican populations suggest an association of higher prenatal fluoride exposure with poorer neurobehavioral development, but whether this association holds for US-based populations is unknown.To examine associations of third trimester maternal urinary fluoride (MUF) with child neurobehavior at age 3 years in the US.This prospective cohort study utilized urine samples archived from 2017 to 2020 and neurobehavioral data assessed from 2020 to 2023 from the Maternal and Developmental Risks from Environmental and Social Stressors (MADRES) pregnancy cohort, which consisted of predominately Hispanic women residing in Los Angeles, California. Cohort eligibility criteria at recruitment included being 18 years of age or older, less than 30 weeks' gestation, and a fluent English or Spanish speaker. Exclusion criteria included having a disability preventing participation or provision of informed consent, being HIV positive or incarcerated, and having a multiple gestation pregnancy. There were 263 mother-child pairs who completed the 3-year study visit. In this analysis, women who reported prenatal smoking were excluded. Data analysis was conducted from October 2022 to March 2024.Specific gravity-adjusted MUF (MUFSG), a biomarker of prenatal fluoride exposure.Neurobehavior was quantified using the Preschool Child Behavior Checklist (CBCL), which included composite scores for Total Problems, Internalizing Problems, and Externalizing Problems. CBCL composite T scores range from 28 to 100. T scores from 60 to 63 are in the borderline clinical range, whereas scores above 63 are in the clinical range. Linear and logistic regression models adjusted for covariates were conducted.A total of 229 mother-child pairs (mean [SD] maternal age, 29.45 [5.67] years; 116 female children [50.7%] and 113 male children [49.3%]) who had MUFSG measured were included in the study. Median (IQR) MUFSG was 0.76 (0.51-1.19) mg/L, and 32 participants (14.0%) had a Total Problems T score in the borderline clinical or clinical range. A 1-IQR (0.68 mg/L) increase in MUFSG was associated with nearly double the odds of the Total Problems T score being in the borderline clinical or clinical range (odds ratio, 1.83; 95% CI, 1.17-2.86; P = .008), as well as with a 2.29-point increase in T score for the Internalizing Problems composite (B = 2.29; 95% CI, 0.47-4.11; P = .01) and a 2.14-point increase in T score for the Total Problems composite (B = 2.14; 95% CI, 0.29-3.98; P = .02).In this prospective cohort study of mother-child pairs in Los Angeles, California, prenatal fluoride exposure was associated with increased neurobehavioral problems. These findings suggest that there may be a need to establish recommendations for limiting fluoride exposure during the prenatal period.
View details for DOI 10.1001/jamanetworkopen.2024.11987
View details for PubMedID 38767917
View details for PubMedCentralID PMC11107298
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Associations of Organophosphate Ester Flame Retardant Exposures during Pregnancy with Gestational Duration and Fetal Growth: The Environmental influences on Child Health Outcomes (ECHO) Program
Environmental Health Perspectives
2024
View details for DOI 10.1289/EHP13182
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Organophosphate ester flame retardant chemicals and maternal depression during pregnancy
Environmental Research
2024
View details for DOI 10.1016/j.envres.2024.119581
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Prenatal exposures to organophosphate ester metabolites and early motor development in the MADRES cohort
Environmental Pollution
2024
View details for DOI 10.1016/j.envpol.2023.123131
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First trimester prenatal metal mixtures, vitamins, and hypertensive disorders of pregnancy in the project viva cohort
Environment International
2024
View details for DOI 10.1016/j.envint.2024.108909
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Prenatal exposures to organophosphate ester metabolite mixtures and children's neurobehavioral outcomes in the MADRES pregnancy cohort.
Environmental health : a global access science source
2023; 22 (1): 66
Abstract
Evidence suggests organophosphate esters (OPEs) are neurotoxic; however, the epidemiological literature remains scarce. We investigated whether prenatal exposures to OPEs were associated with child neurobehavior in the MADRES cohort.We measured nine OPE metabolites in 204 maternal urine samples (gestational age at collection: 31.4 ± 1.8 weeks). Neurobehavior problems were assessed among 36-month-old children using the Child Behavior Checklist's (CBCL) three composite scales [internalizing, externalizing, and total problems]. We examined associations between tertiles of prenatal OPE metabolites (> 50% detection) and detect/non-detect categories (< 50% detection) and CBCL composite scales using linear regression and generalized additive models. We also examined mixtures for widely detected OPEs (n = 5) using Bayesian kernel machine regression.Maternal participants with detectable versus non-detectable levels of bis(2-methylphenyl) phosphate (BMPP) had children with 42% (95% CI: 4%, 96%) higher externalizing, 45% (-2%, 114%) higher internalizing, and 35% (3%, 78%) higher total problems. Participants in the second versus first tertile of bis(butoxethyl) phosphate (BBOEP) had children with 43% (-1%, 109%) higher externalizing scores. Bis(1-chloro-2-propyl) phosphate (BCIPP) and child sex had a statistically significant interaction in internalizing (p = 0.02) and total problems (p = 0.03) models, with 120% (23%, 295%) and 57% (6%, 134%) higher scores in the third versus first BCIPP tertile among males. Among females, detectable vs non-detectable levels of prenatal BMPP were associated with 69% higher externalizing scores (5%, 170%) while the third versus first tertile of prenatal BBOEP was associated with 45% lower total problems (-68%, -6%). Although the metabolite mixture and each CBCL outcome had null associations, we observed marginal associations between di-n-butyl phosphate and di-isobutyl phosphate (DNBP + DIBP) and higher internalizing scores (0.15; 95% CrI: -0.02, 0.32), holding other metabolites at their median.Our results generally suggest adverse and sex-specific effects of prenatal exposure to previously understudied OPEs on neurobehavioral outcomes in 36-month children, providing evidence of potential OPE neurotoxicity.
View details for DOI 10.1186/s12940-023-01017-3
View details for PubMedID 37737180
View details for PubMedCentralID PMC10515433
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Sex-specific effects of prenatal organophosphate ester (OPE) metabolite mixtures and adverse infant birth outcomes in the maternal and developmental risks from environmental and social stressors (MADRES) pregnancy cohort
ENVIRONMENTAL RESEARCH
2023; 226: 115703
Abstract
Organophosphate esters (OPEs) are used as flame retardants and plasticizers in various consumer products. Limited prior research suggests sex-specific effects of prenatal OPE exposures on fetal development. We evaluated overall and sex-specific associations between prenatal OPE exposures and gestational age (GA) at birth and birthweight for gestational age (BW for GA) z-scores among the predominately low-income, Hispanic MADRES cohort.Nine OPE metabolite concentrations were measured in 421 maternal urine samples collected during a third trimester visit (GA = 31.5 ± 2.0 weeks). We examined associations between single urinary OPE metabolites and GA at birth and BW for GA z-scores using linear regression models and Generalized Additive Models (GAMs) and effects from OPE mixtures using Bayesian Kernel Machine Regression (BKMR). We also assessed sex-specific differences in single metabolite analyses by evaluating statistical interactions and stratifying by sex.We did not find significant associations between individual OPE metabolites and birth outcomes in the full infant sample; however, we found that higher bis(1,3-dichloro-2-propyl) phosphate (BDCIPP) was associated with earlier GA at birth among male infants (p = 0.04), and a nonlinear, inverted U-shape association between the sum of dibutyl phosphate and di-isobutyl phosphate (DNBP + DIBP) and GA at birth among female infants (p = 0.03). In mixtures analysis, higher OPE metabolite mixture exposures was associated with lower GA at birth, which was primarily driven by female infants. No associations were observed between OPE mixtures and BW for GA z-scores.Higher BDCIPP and DNBP + DIBP concentrations were associated with earlier GA at birth among male and female infants, respectively. Higher exposure to OPE mixtures was associated with earlier GA at birth, particularly among female infants. However, we saw no associations between prenatal OPEs and BW for GA. Our results suggest sex-specific impacts of prenatal OPE exposures on GA at birth.
View details for DOI 10.1016/j.envres.2023.115703
View details for Web of Science ID 000959352700001
View details for PubMedID 36934865
View details for PubMedCentralID PMC10101931
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COVID-19 Pandemic Experiences and Symptoms of Pandemic-Associated Traumatic Stress Among Mothers in the US
JAMA NETWORK OPEN
2022; 5 (12): e2247330
Abstract
The primary outcomes of the COVID-19 pandemic on the mental health of women with children remain largely unknown.To identify and describe clusters of mothers of children participating in the Environmental influences on Child Health Outcomes (ECHO) Program that characterize pandemic-associated hardships, coping mechanisms, and behaviors, and to evaluate associations between pandemic-associated hardships, coping strategies, and behavior changes with pandemic-associated traumatic stress symptoms.This multicenter cohort study investigated experiences during the COVID-19 pandemic between April 2020 and August 2021 among maternal caregivers of children participating in the ECHO Program. Data from self-identified mothers of ECHO-enrolled children from 62 US cohorts were included in analyses. Data were analyzed from November 2021 to July 2022.The primary exposures were pandemic-associated changes in mothers' health, health care utilization, work and finances, coping strategies, and health-associated behaviors. Exposures were assessed via a self-reported questionnaire designed by ECHO investigators.The primary outcome was the total symptoms score of pandemic-associated traumatic stress (PTS), defined as the number of items endorsed at least sometimes or more frequently, from a 10-item self-report measure.The study surveyed 11 473 mothers (mean [SD] age, 37.8 [7.4] years; 342 American Indian [2.98%], 378 Asian [3.29%], 1701 Black [14.83%], and 7195 White [62.71%]; 2184 with Hispanic/Latina ethnicity [19.04%]) and identified 2 clusters that best characterized their COVID-19 pandemic experiences-one characterized by higher life disruptions (eg, to work and health care), higher social isolation, more coping behaviors to mitigate the outcomes of the pandemic, and more changes to their health behavior routines (high change [1031 mothers]) and the other characterized by lower changes (low change [3061 mothers]). The high change cluster was more socioeconomically advantaged and reported higher PTS (mean [SD] number of symptoms, 3.72 [2.44] vs 2.51 [2.47]). Across both clusters, higher pandemic-associated hardships, coping mechanisms, and behavior changes were associated with higher PTS, and these associations were greater in the low change cluster.In this study of more than 11 000 US mothers, associations between socioeconomic factors, stressful life events, and mental health sequelae were complex. Accordingly, programs, policies, and practices targeting mental health during public health crises such as the COVID-19 pandemic should consider the range and configuration of hardships in designing the most effective interventions to mitigate long-term outcomes.
View details for DOI 10.1001/jamanetworkopen.2022.47330
View details for Web of Science ID 000919589300008
View details for PubMedID 36525271
View details for PubMedCentralID PMC9856510
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Perceived vulnerability to immigration policies among postpartum Hispanic/Latina women in the MADRES pregnancy cohort before and during the COVID-19 pandemic
WOMENS HEALTH
2022; 18: 17455057221125103
Abstract
Research suggests that perceived immigration policy vulnerability has important health implications. Coupled with the mental and physical stressors accompanying the postpartum period and a growing awareness of the discrimination and structural racism experienced by marginalized communities globally, the coronavirus disease 2019 period may have exacerbated stress among vulnerable populations, specifically postpartum Hispanic/Latina women. This study evaluated perceived immigration policy vulnerability (i.e. discrimination, social isolation, and family threats) in early postpartum Hispanic/Latina women in Los Angeles before and during the coronavirus disease 2019 pandemic.The Perceived Immigration Policy Effects Scale (PIPES) was administered cross-sectionally at 1 month postpartum to 187 Hispanic/Latina women in the MADRES cohort. Respondents between September 2018 and March 2020 were classified as "pre-pandemic" (N = 128), between March 2020 and July 2020 as "early pandemic" (N = 38), and between August 2020 and November 2021 as "later pandemic" (N = 21). Average PIPES subscale scores were dichotomized into "higher" and "lower" groups (⩽median, >median) and logistic regression models were performed.Approximately half of participants had incomes of <$50,000 (50.3%) and were Latin American born (54.6%). After adjusting for age, nativity, education, income, postpartum distress, and employment status, early pandemic respondents had 5.05 times the odds of a higher score on the perceived discrimination subscale (95% CI: 1.81, 14.11), 6.47 times the odds of a higher score on the social isolation subscale (95% CI: 2.23, 18.74), 2.66 times the odds of a higher score on the family threats subscale (95% CI: 0.97, 7.32), and 3.36 times the odds of a higher total score (95% CI: 1.19, 9.51) when compared to pre-pandemic respondents. There were no significant subscale score differences between later pandemic and pre-pandemic periods.Higher perceived immigration policy vulnerability was reported among postpartum women during the early coronavirus disease 2019 pandemic versus pre-pandemic periods. This suggests greater social inequities during the early pandemic period.
View details for DOI 10.1177/17455057221125103
View details for Web of Science ID 000859851400001
View details for PubMedID 36148937
View details for PubMedCentralID PMC9511002
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Household pesticide exposures and infant gross motor development in the MADRES cohort
PAEDIATRIC AND PERINATAL EPIDEMIOLOGY
2022; 36 (2): 220-229
Abstract
The development of motor skills in infancy is a vital neurodevelopmental milestone. Although previous studies have explored the neurotoxic effects of agricultural pesticides on infants' motor development, limited research has examined early postnatal household pesticide use on infants' motor development, particularly among urban communities.This study examined the association between early postnatal household pesticide use and infants' gross and fine motor development at 6 months of age.Questionnaires were administered via telephone to 296 mother-infant dyads in the Maternal and Developmental Risks from Environmental and Social Stressors (MADRES) pregnancy cohort. Early life household pesticide use was assessed via questionnaire administered when infants turned 3 months old and gross and fine motor development was assessed by the Ages and Stages Questionnaire (ASQ-3) at 6 months old. Infant gross motor scores were reverse coded so that higher scores indicated lower gross motor performance. Negative binomial regressions were performed to assess the relationship between household pesticide use and infant gross motor development.Infants were predominantly Hispanic (78.7%) and full term (gestational age at birth: 39.0 ± 1.9 weeks), with 22.3% of maternal participants reporting household use of rodent and insect pesticides. Adjusting for recruitment site, maternal age, ethnicity, household income, education, infant corrected age, infant sex, and home type, infants with maternal-reported household use of rodent and insect pesticides had 1.30 times higher expected gross motor scores (95% confiidence interval 1.05, 1.61) than infants with no reported use of household pesticides, with higher scores indicating reduced gross motor performance.Our results suggest household use of rodent and insect pesticides may harm infants' gross motor development in early childhood. Future research should evaluate the impact of specific household chemicals in infant biospecimens and their associations with infant motor development to confirm these findings.
View details for DOI 10.1111/ppe.12850
View details for Web of Science ID 000735410300001
View details for PubMedID 34964501
View details for PubMedCentralID PMC8881403
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Prenatal ambient air pollution and maternal depression at 12 months postpartum in the MADRES pregnancy cohort
ENVIRONMENTAL HEALTH
2021; 20 (1): 121
Abstract
Depression is the leading cause of mental health-related morbidity and affects twice as many women as men. Hispanic/Latina women in the US have unique risk factors for depression and they have lower utilization of mental health care services. Identifying modifiable risk factors for maternal depression, such as ambient air pollution, is an urgent public health priority. We aimed to determine whether prenatal exposure to ambient air pollutants was associated with maternal depression at 12 months after childbirth.One hundred eighty predominantly low-income Hispanic/Latina women participating in the ongoing MADRES cohort study in Los Angeles, CA were followed from early pregnancy through 12 months postpartum through a series of phone questionnaires and in-person study visits. Daily prenatal ambient pollutant estimates of nitrogen dioxide (NO2), ozone (O3), and particulate matter (PM10 and PM2.5) were assigned to participant residences using inverse-distance squared spatial interpolation from ambient monitoring data. Exposures were averaged for each trimester and across pregnancy. The primary outcome measure was maternal depression at 12 months postpartum, as reported on the 20-item Center for Epidemiologic Studies-Depression (CES-D) scale. We classified each participant as depressed (n = 29) or not depressed (n = 151) based on the suggested cutoff of 16 or above (possible scores range from 0 to 60) and fitted logistic regression models, adjusting for potential confounders.We found over a two-fold increased odds of depression at 12 months postpartum associated with second trimester NO2 exposure (OR = 2.63, 95% CI: 1.41-4.89) and pregnancy average NO2 (OR = 2.04, 95% CI: 1.13-3.69). Higher second trimester PM2.5 exposure also was associated with increased depression at 12 months postpartum (OR = 1.56, 95% CI: 1.01-2.42). The effect for second trimester PM10 was similar and was borderline significant (OR = 1.58, 95% CI: 0.97-2.56).In a low-income cohort consisting of primarily Hispanic/Latina women in urban Los Angeles, we found that prenatal ambient air pollution, especially mid-pregnancy NO2 and PM2.5, increased the risk of depression at 12 months after childbirth. These results underscore the need to better understand the contribution of modifiable environmental risk factors during potentially critical exposure periods.
View details for DOI 10.1186/s12940-021-00807-x
View details for Web of Science ID 000722995100001
View details for PubMedID 34838014
View details for PubMedCentralID PMC8626870