Zhanghua Chen

BackgroundPer- and polyfluoroalkyl substances (PFAS) may impair bone development in adolescence, which impacts life-long bone health. No previous studies have examined prospective associations of individual PFAS and their mixture with bone mineral density (BMD) changes in Hispanic young persons, a population at high risk of osteoporosis in adulthood.ObjectivesTo examine associations of individual PFAS and PFAS mixtures with longitudinal changes in BMD in an adolescent Hispanic cohort and examine generalizability of findings in a mixed-ethnicity young adult cohort (58.4% Hispanic).MethodsOverweight/obese adolescents from the Study of Latino Adolescents at Risk of Type 2 Diabetes (SOLAR; n = 304; mean follow-up = 1.4 years) and young adults from the Southern California Children's Health Study (CHS; n = 137; mean follow-up = 4.1 years) were included in this study. Plasma PFAS were …

OBJECTIVE Prediabetes in young people is an emerging epidemic that disproportionately impacts Hispanic populations. We aimed to develop a metabolite-based prediction model for prediabetes in young people with overweight/obesity at risk for type 2 diabetes. RESEARCH DESIGN AND METHODS In independent, prospective cohorts of Hispanic youth (discovery; n = 143 without baseline prediabetes) and predominately Hispanic young adults (validation; n = 56 without baseline prediabetes), we assessed prediabetes via 2-h oral glucose tolerance tests. Baseline metabolite levels were measured in plasma from a 2-h postglucose challenge. In the discovery cohort, least absolute shrinkage and selection operator regression with a stability selection procedure was used to identify robust predictive metabolites for prediabetes. Predictive performance was evaluated in the discovery …

BackgroundPer- and polyfluoroalkyl substances (PFAS) are pollutants linked to adverse health effects. Diet is an important source of PFAS exposure, yet it is unknown how diet impacts longitudinal PFAS levels.ObjectiveTo determine if dietary intake and food sources were associated with changes in blood PFAS concentrations among Hispanic young adults at risk of metabolic diseases.MethodsPredominantly Hispanic young adults from the Children’s Health Study who underwent two visits (CHS; n = 123) and young adults from NHANES 2013–2018 who underwent one visit (n = 604) were included. Dietary data at baseline was collected using two 24-hour dietary recalls to measure individual foods and where foods were prepared/consumed (home/restaurant/fast-food). PFAS were measured in blood at both visits in CHS and cross-sectionally in NHANES. In CHS, multiple linear regression assessed associations of …

ImportanceFamily socioeconomic status has been associated with autism spectrum disorder (ASD) diagnoses. Less is known regarding the role of neighborhood disadvantage in the United States, particularly when children have similar access to health insurance.ObjectiveTo evaluate the association between neighborhood disadvantage and the diagnosis of ASD and potential effect modification by maternal and child demographic characteristics.Design, Setting, and ParticipantsThis cohort study examined a retrospective birth cohort from Kaiser Permanente Southern California (KPSC), an integrated health care system. Children born in 2001 to 2014 at KPSC were followed up through KPSC membership records. Electronic medical records were used to obtain an ASD diagnosis up to December 31, 2019, or the last follow-up. Data were analyzed from February 2022 to September 2023.ExposureSocioeconomic …

Background Experimental evidence indicates that exposure to certain pollutants is associated with liver damage. Per- and polyfluoroalkyl substances (PFAS) are persistent synthetic chemicals widely used in industry and consumer products and bioaccumulate in food webs and human tissues, such as the liver. Objective The objective of this study was to conduct a systematic review of the literature and meta-analysis evaluating PFAS exposure and evidence of liver injury from rodent and epidemiological studies. Methods PubMed and Embase were searched for all studies from earliest available indexing year through 1 December 2021 using keywords corresponding to PFAS exposure and liver injury. For data synthesis, results were limited to studies in humans and rodents assessing the following indicators of liver injury: serum alanine aminotransferase (ALT), nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, or steatosis. For human …

The assessment of “omics” signatures may contribute to personalized medicine and precision nutrition. However, the existing literature is still limited in the homogeneity of participants’ characteristics and in limited assessments of integrated omics layers. Our objective was to use post-prandial metabolomics and fasting proteomics to identify biological pathways and functions associated with diet quality in a population of primarily Hispanic young adults. We conducted protein and metabolite-wide association studies and functional pathway analyses to assess the relationships between a priori diet indices, Healthy Eating Index-2015 (HEI) and Dietary Approaches to Stop Hypertension (DASH) diets, and proteins (n = 346) and untargeted metabolites (n = 23,173), using data from the MetaAIR study (n = 154, 61% Hispanic). Analyses were performed for each diet quality index separately, adjusting for demographics and BMI. Five proteins (ACY1, ADH4, AGXT, GSTA1, F7) and six metabolites (undecylenic acid, betaine, hyodeoxycholic acid, stearidonic acid, iprovalicarb, pyracarbolid) were associated with both diets (p < 0.05), though none were significant after adjustment for multiple comparisons. Overlapping proteins are involved in lipid and amino acid metabolism and in hemostasis, while overlapping metabolites include amino acid derivatives, bile acids, fatty acids, and pesticides. Enriched biological pathways were involved in macronutrient metabolism, immune function, and oxidative stress. These findings in young Hispanic adults contribute to efforts to develop precision nutrition and medicine for diverse populations.

To assess cardiometabolic profiles and proteomics to identify biomarkers associated with the metabolically healthy and unhealthy obesity. Young adults (N = 156) enrolled were classified as not having obesity, metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUHO) based on NCEP ATP-III criteria. Plasma proteomics at study entry were measured using Olink Cardiometabolic Explore panel. Linear regression was used to assess associations between proteomics and obesity groups as well as cardiometabolic traits of glucose, insulin, and lipid profiles at baseline and follow-up visits. Enriched biological pathways were further identified based on the significant proteomic features. Among the baseline 95 (61%) and 61 (39%) participants classified as not having obesity and having obesity (8 MHO and 53 MUHO), respectively. Eighty of the participants were followed-up with an average 4.6 …

BackgroundPubertal growth patterns correlate with future health outcomes. However, the genetic mechanisms mediating growth trajectories remain largely unknown. Here, we modeled longitudinal height growth with Super-Imposition by Translation And Rotation (SITAR) growth curve analysis on ~ 56,000 trans-ancestry samples with repeated height measurements from age 5 years to adulthood. We performed genetic analysis on six phenotypes representing the magnitude, timing, and intensity of the pubertal growth spurt. To investigate the lifelong impact of genetic variants associated with pubertal growth trajectories, we performed genetic correlation analyses and phenome-wide association studies in the Penn Medicine BioBank and the UK Biobank.ResultsLarge-scale growth modeling enables an unprecedented view of adolescent growth across contemporary and 20th-century pediatric cohorts. We identify …

The preconception period is a critical window for gametogenesis, therefore preconception exposure to air pollutants may have long-term effects on children. We systematically reviewed epidemiological evidence concerning the effects of preconception ambient air pollution exposure on children's health outcomes and identified research gaps for future investigations. We searched PubMed and Web of Science from journal inception up to October 2022 based on an established protocol (PROSPERO: CRD42022277608). We then identified 162 articles based on searching strategy, 22 of which met the inclusion criteria. Studies covered a wide range of health outcomes including birth defects, preterm birth, birthweight, respiratory outcomes, and developmental outcomes. Findings suggested that exposure to outdoor air pollutants during maternal preconception period were associated with various health outcomes, of …

BackgroundThere is increasing evidence for adverse health effects associated with aircraft-emitted particulate matter (PM) exposures, which are largely in the ultrafine (PM0.1) size fraction, but no previous study has examined neurodevelopmental outcomes.ObjectiveTo assess associations between maternal exposure to aircraft ultrafine particles (UFP) during pregnancy and offspring autism spectrum disorder (ASD) diagnosis.MethodsThis large, representative cohort study included 370,723 singletons born in a single healthcare system. Demographic data, maternal health information, and child’s ASD diagnosis by age 5 were extracted from electronic medical records. Aircraft exposure estimates for PM0.1 were generated by the University of California Davis/California Institute of Technology Source Oriented Chemical Transport model. Cox proportional hazard models were used to assess associations between …

BACKGROUND AND AIM Whether COVID-19 vaccination affects the known adverse effects of air pollution exposure is unknown. We aim to investigate associations of air pollution exposure and COVID-19 vaccine with the risk of COVID-19-related hospitalizations. METHOD This study included Kaiser Permanente Southern California (KPSC) health plan members age = 12 years diagnosed with COVID-19 from 7/1/2021 to 8/31/2021 when the Delta variant was the dominant strain. 1-year and 1-month averaged ambient air pollutant (PM2.5 and NO2) exposures before COVID-19 diagnosis were estimated based on residential address history. COVID-19 vaccination status was retrieved from the electronic medical records. Vaccination status before COVID-19 diagnosis was categorized into none, partially vaccinated (1 dose Pfizer-BioNTech or Moderna), or fully vaccinated (1 Johnson and Johnson or 2 doses Pfizer …

Few studies have examined the association between greenness exposure and birth outcomes. This study aims to identify critical exposure time windows during preconception and pregnancy for the association between greenness exposure and birth weight. A cohort of 13 890 pregnant women and newborns in Shanghai, China from 2016–2019 were included in the study. We assessed greenness exposure using Normalized Difference Vegetation Index (NDVI) during the preconception and gestational periods, and evaluated the association with term birthweight, birthweight z-score, small-for-gestational age, and large-for-gestational age using linear and logistic regressions adjusting for key maternal and newborn covariates. Ambient temperature, relative humidity, ambient levels of fine particles (PM 2.5) and nitrogen dioxide (NO 2) assessed during the same period were adjusted for as sensitivity analyses …

MethodsThis study cohort included 50,010 KPSC (Kaiser Permanente Southern California) health plan members aged 12 years or older diagnosed with COVID-19 from July 1, 2021 to August 31, 2021. KPSC is an integrated healthcare system in which members with medical procedures or with COVID-19 symptoms require COVID-19 testing. COVID-19 tests were also administered for patients by request. Self-reported positive tests were captured in the KPSC electronic medical records (EMR). The outcome was hospitalization within 30 days after COVID-19 diagnosis date with COVID-19–related reason for hospitalization. The study was approved by the KPSC Institutional Review Board with an informed consent waiver.

Mounting evidence suggests that air pollution influences lipid metabolism and dyslipidemia. However, the metabolic mechanisms linking air pollutant exposure and altered lipid metabolism is not established. In year 2014–2018, we conducted a cross-sectional study on 136 young adults in southern California, and assessed lipid profiles (triglycerides, total cholesterol, high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein (LDL)-cholesterol, very-low-density lipoprotein (VLDL)-cholesterol), and untargeted serum metabolomics using liquid chromatography-high-resolution mass spectrometry, and one-month and one-year averaged exposures to NO2, O3, PM2.5 and PM10 air pollutants at residential addresses. A metabolome-wide association analysis was conducted to identify metabolomic features associated with each air pollutant. Mummichog pathway enrichment analysis was used to assess altered …

BACKGROUND AND AIM This study aims to assess maternal factors (age, breastfeeding and weight) that may influence plasma concentrations of persistent organic pollutants (POPs) in women from pregnancy to postpartum period. METHOD 97 Hispanic women (mean ± SD = 30.47 ± 5.67 years) with gestational diabetes mellitus (GDM) were enrolled in this study. Plasma concentrations of 41 POPs including 21 polychlorinated biphenyls (PCBs), 7 organochlorine pesticides (OCPs), 5 polybrominated diphenyl ethers (PBDEs), 2,2’,4,4’,5,5’-hexabromobiphenyl (BB-153), 7 perfluoroalkyl substances (PFASs) were measured from archived samples collected at 3rd trimester of pregnancy and 15-60 months postpartum. Multivariate linear regression model was used to assess associations of 1) maternal age and pre-pregnancy weight with the POPs concentrations at 3rd trimester; 2) maternal age, weight, and …

Methods: MetaAir study participants (n= 154, 61% Hispanic) completed a clinical visit between 2014-2018. The Healthy Eating Index-2015, Dietary Approaches to Stop Hypertension, and Mediterranean diet scores were calculated from two 24-hour dietary recalls. Targeted proteomics (346 proteins) were measured in a cardiometabolic panel and untargeted metabolomics were assessed using LC-HRMS. The results of metabolite-and protein-wide association studies were used in functional pathway analysis with MetaboAnalyst and Reactome, respectively. Analyses were performed for each diet index separately, adjusting for demographics and BMI.Results: 16.4% of metabolite and 20% of protein features were significantly (p< 0.05) associated with at least one diet index. Two annotated metabolites (L-methionine, prostaglandin F2α) and four proteins (ACY1, ADH4, AGXT, GSTA1) were associated with all three dietary indices. These features are involved in amino acid metabolism, liver function, and inflammation, and are involved in biological pathways like arachidonic acid metabolism, prostaglandin formation, and biological oxidations. Overall, 21 metabolomics and 84 proteomics pathways were associated with at least one diet index and had similar functions, including those related to cell signaling and growth, hemostasis, immune function, and hormone regulation.Discussion: Adherence to healthy dietary patterns influences biological pathways involved in disease development and progression. Omics analyses may provide information about the mechanisms by which a healthy diet improves human health.

BackgroundTraffic-related air pollution exposure is associated with increased risk of autism spectrum disorder (ASD). It is unknown whether carbonaceous material from vehicular tailpipe emissions or redox-active non-tailpipe metals, eg. from tire and brake wear, are responsible. We assessed ASD associations with fine particulate matter (PM2.5) tracers of tailpipe (elemental carbon [EC] and organic carbon [OC]) and non-tailpipe (copper [Cu]; iron [Fe] and manganese [Mn]) sources during pregnancy in a large cohort.MethodsThis retrospective cohort study included 318,750 children born in Kaiser Permanente Southern California (KPSC) hospitals during 2001–2014, followed until age 5. ASD cases were identified by ICD codes. Monthly estimates of PM2.5 and PM2.5 constituents EC, OC, Cu, Fe, and Mn with 4 km spatial resolution were obtained from a source-oriented chemical transport model. These exposures …

Gastrointestinal disturbances (GIDs) are relatively common in children diagnosed with autism spectrum disorder (ASD). This study assessed associations between maternal obesity, diabetes, preeclampsia, and asthma and likelihood of ASD with GIDs. This retrospective cohort study included 308,536 mother–child pairs of singletons born between 2001 and 2014 in a single integrated health care system. Social demographics, maternal health conditions during pregnancy, and child’s ASD and/or GID diagnosis by age 5 were extracted from electronic medical records. Child’s outcome was classified as: no ASD no GIDs; no ASD with GIDs; ASD no GIDs; and ASD with GIDs. Multinomial logistic regression was used to estimate odds ratios of child’s outcomes associated with maternal exposures, adjusting for covariates. Compared to children with neither disorder, each maternal condition was associated with higher …

BACKGROUND AND AIM Prenatal exposure to fine particulate matter (PM₂.₅), especially during second trimester, has been associated with lower birth weight in Maternal and Developmental Risks from Environmental and Social Stressors (MADRES) study. This study aims to investigate potential maternal metabolic pathways in third trimester mediating the association between second-trimester PM₂.₅ exposure and lower birth weight. METHOD Based on the ongoing MADRES study in Los Angeles, 421 maternal serum samples collected at third trimester were analyzed for untargeted metabolomics using LC-MS. Daily estimates of PM₂.₅ concentrations were assigned to each participant’s residential address using inverse-distance-squared weighted spatial interpolation and calculated as second-trimester averages. Birth weight and covariates were retrieved from electronic medical records or questionnaires …

BackgroundFew studies have assessed air pollution exposure association with birthweight during both preconception and gestational periods.MethodsLeveraging a preconception cohort consisting of 14220 pregnant women and newborn children in Shanghai, China during 2016–2018, we aim to assess associations of NO2 and PM2.5 exposure, derived from high-resolution spatial-temporal models, during preconception and gestational periods with outcomes including term birthweight, birthweight Z-score, small-for-gestational age (SGA) and large-for-gestational age (LGA). Linear and logistic regressions were used to estimate 3-month preconception and trimester-averaged air pollution exposure associations; and distributed lag models (DLM) were used to identify critical exposure windows at the weekly resolution from preconception to delivery. Two-pollutant models and children’s sex-specific associations were …