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Phthalates and attributable mortality: A population-based longitudinal cohort study and cost analysis

Trasande, Leonardo; Liu, Buyun; Bao, Wei
CONTEXT/BACKGROUND:Accelerating evidence of endocrine-related morbidity has raised alarm about the ubiquitous use of phthalates in the human environment, but studies have not directly evaluated mortality in relation to these exposures. OBJECTIVES/OBJECTIVE:To evaluate associations of phthalate exposure with mortality, and quantify attributable mortality and lost economic productivity in 2013-4 among 55-64 year olds. DESIGN/METHODS:This nationally representative cohort study included 5303 adults aged 20 years or older who participated in the US National Health and Nutrition Examination Survey 2001-2010 and provided urine samples for phthalate metabolite measurements. Participants were linked to mortality data from survey date through December 31, 2015. Data analyses were conducted in July 2020. MAIN OUTCOME MEASURES/METHODS:Mortality from all causes, cardiovascular disease, and cancer. RESULTS:Multivariable models identified increased mortality in relation to high-molecular weight (HMW) phthalate metabolites, especially those of di-2-ethylhexylphthalate (DEHP). Hazard ratios (HR) for continuous HMW and DEHP metabolites were 1.14 (95% CI 1.06-1.23) and 1.10 (95% CI 1.03-1.19), respectively, with consistently higher mortality in the third tertile (1.48, 95% CI 1.19-1.86; and 1.42, 95% CI 1.13-1.78). Cardiovascular mortality was significantly increased in relation to a prominent DEHP metabolite, mono-(2-ethyl-5-oxohexyl)phthalate. Extrapolating to the population of 55-64 year old Americans, we identified 90,761-107,283 attributable deaths and $39.9-47.1 billion in lost economic productivity. CONCLUSIONS:In a nationally representative sample, phthalate exposures were associated with all-cause and cardiovascular mortality, with societal costs approximating $39 billion/year or more. While further studies are needed to corroborate observations and identify mechanisms, regulatory action is urgently needed.
PMID: 34654571
ISSN: 1873-6424
CID: 5062022

COVID-19 Symptoms and Diagnoses among a Sociodemographically Diverse Cohort of Children from New York City: Lessons from the First Wave, Spring 2020

Kahn, Linda G; Ghassabian, Akhgar; Jacobson, Melanie H; Yu, Keunhyung; Trasande, Leonardo
Early in the pandemic, in the North American epicenter, we investigated associations between sociodemographic factors and rates of pediatric COVID-19 diagnoses in a non-clinical setting and whether symptoms varied by child age. From 20 April-31 August 2020, COVID-19-related data were collected on 2694 children aged ≤ 18 years living in households participating in the New York University Children's Health and Environment Study. We examined differences in rates of subjective and objective diagnoses according to sociodemographic characteristics and differences in reported symptoms by child age. Children of women who were non-Hispanic White, had private health insurance, higher income, or more education were more likely to be diagnosed via WHO criteria or healthcare provider. Children of women who were Hispanic or Asian, reported low income, had less education, or were/lived with an essential worker were more likely to test positive. Older children were less likely to experience cough or runny nose and more likely to experience muscle/body aches, sore throat, headache, and loss of smell or taste than younger children. In conclusion, relying on subjective disease ascertainment methods, especially in the early stage of an outbreak when testing is not universally available, may misrepresent the true prevalence of disease among sociodemographic subgroups. Variations in symptoms by child age should be considered when determining diagnostic criteria.
PMID: 34831640
ISSN: 1660-4601
CID: 5063892

Feeding Problems as an Indicator of Developmental Delay in Early Childhood

Putnick, Diane L; Bell, Erin M; Ghassabian, Akhgar; Robinson, Sonia L; Sundaram, Rajeshwari; Yeung, Edwina
OBJECTIVE:To determine if feeding problems are an indicator of developmental delay. STUDY DESIGN/METHODS:percentile across time. The Battelle Developmental Inventory (BDI-2) assessed development in 5 domains for a subset of children at 4 years. RESULTS:In adjusted analyses, feeding problems (per point increase) were increasingly associated with six ASQ domains from 18 months (Odds Ratios (ORs) ranged from 1.30 to 1.98) to 24 months (ORs = 2.07 - 2.69) to 30 months (ORs = 3.90 - 5.64). Compared with children who never experienced feeding problems, children who experienced high feeding problems at one or two time points were more than twice as likely to fail all ASQ domains (ORs = 2.10 - 2.50), and children who experienced high feeding problems at all three time points were four or more times as likely to fail all ASQ domains (ORs = 3.94 - 5.05). Children with one-point higher feeding problems at 30 months scored 3-4 points lower on all BDI-2 domains at 4 years. CONCLUSIONS:Frequent feeding problems, especially those that persist into the third year, could be used to identify children at risk for developmental delay for more targeted screening.
PMID: 34774577
ISSN: 1097-6833
CID: 5048832

Exposure to environmental chemicals and perinatal psychopathology

Jacobson, Melanie H; Ghassabian, Akhgar; Gore, Andrea C; Trasande, Leonardo
Women are nearly twice as likely to develop mood disorders compared with men, and incidence is greatest during reproductive transitions, including pregnancy and postpartum. Because these periods are characterized by dramatic hormonal and physiologic changes, there is heightened susceptibility to external factors, such as exposure to environmental toxicants, which may play a role in maternal psychopathology. The purpose of this scoping review was to provide an overview of studies conducted in humans and animal models on the effects of nonoccupational exposure to environmental chemicals on maternal psychopathology during the perinatal period. The largest number of studies examined exposure to environmental tobacco smoke and antenatal depression and showed consistently positive findings, although more prospective studies using biomarkers for exposure assessment are needed. The few studies examining persistent organic pollutants such as polybrominated diphenyl ethers and perinatal depression were consistent in showing associations with increased depressive symptoms. Results were mixed for exposure to heavy metals and non-persistent chemicals, but a strong literature in animal models supported an association between bisphenols and phthalates and reduced maternal behavior and care of pups after parturition. Biological mechanisms may include endocrine disruption, neurotransmitter system impairment, alterations in gene expression, and immune activation and inflammation. Additional longitudinal studies that include biospecimen collection are essential to furthering the understanding of how environmental toxicants during pregnancy may affect perinatal psychopathology and the underlying mechanisms of action. Future work should also leverage the parallels between animal and human maternal behavior, thereby highlighting the opportunity for multidisciplinary work in this avenue.
PMID: 34774531
ISSN: 1873-2968
CID: 5048822

Occurrence of Polyethylene Terephthalate and Polycarbonate Microplastics in Infant and Adult Feces

Zhang, Junjie; Wang, Lei; Trasande, Leonardo; Kannan, Kurunthachalam
Although human exposure to microplastics (MPs) and the health effects thereof are a global concern, little is known about the magnitude of exposure. In this study, we quantitatively determined the concentrations of polyethylene terephthalate (PET) and polycarbonate (PC) MPs in three meconium and six infant and 10 adult feces samples collected from New York State. PET and PC MPs were found in some meconium samples (at concentration ranges from below the limit of quantification [<LOQ] to 12,000 and <LOQ-110 ng/g dry weight, respectively) and all infant stool specimens (PET: 5700-82,000 ng/g, median, 36,000 ng/g; PC: 49-2100 ng/g, median, 78 ng/g). They were also found in most (PET) or all (PC) adult stool samples but at concentrations an order of magnitude lower than in infants for PET MPs (<LOQ-16,000 ng/g, median, 2600 ng/g). The estimated mean daily exposures from the diet of infants to PET and PC MPs were 83,000 and 860 ng/kg body weight per day, respectively, which were significantly higher than those of adults (PET: 5800 ng/kg-bw/day; PC: 200 ng/kg-bw/d). Our study suggests that infants are exposed to higher levels of MPs than adults.
ISSN: 2328-8930
CID: 5055812

Disparities in Risks of Inadequate and Excessive Intake of Micronutrients during Pregnancy

Sauder, Katherine A; Harte, Robyn N; Ringham, Brandy M; Guenther, Patricia M; Bailey, Regan L; Alshawabkeh, Akram; Cordero, José F; Dunlop, Anne L; Ferranti, Erin P; Elliott, Amy J; Mitchell, Diane C; Hedderson, Monique M; Avalos, Lyndsay A; Zhu, Yeyi; Breton, Carrie V; Chatzi, Leda; Ran, Jin; Hertz-Picciotto, Irva; Karagas, Margaret R; Sayarath, Vicki; Hoover, Joseph; MacKenzie, Debra; Lyall, Kristen; Schmidt, Rebecca J; O'Connor, Thomas G; Barrett, Emily S; Switkowski, Karen M; Comstock, Sarah S; Kerver, Jean M; Trasande, Leonardo; Tylavsky, Frances A; Wright, Rosalind J; Kannan, Srimathi; Mueller, Noel T; Catellier, Diane J; Glueck, Deborah H; Dabelea, Dana
BACKGROUND:Inadequate or excessive intake of micronutrients in pregnancy has potential to negatively impact maternal/offspring health outcomes. OBJECTIVE:The aim was to compare risks of inadequate or excessive micronutrient intake in diverse females with singleton pregnancies by strata of maternal age, race/ethnicity, education, and prepregnancy BMI. METHODS:Fifteen observational cohorts in the US Environmental influences on Child Health Outcomes (ECHO) Consortium assessed participant dietary intake with 24-h dietary recalls (n = 1910) or food-frequency questionnaires (n = 7891) from 1999-2019. We compared the distributions of usual intake of 19 micronutrients from food alone (15 cohorts; n = 9801) and food plus dietary supplements (10 cohorts with supplement data; n = 7082) to estimate the proportion with usual daily intakes below their age-specific daily Estimated Average Requirement (EAR), above their Adequate Intake (AI), and above their Tolerable Upper Intake Level (UL), overall and within sociodemographic and anthropometric subgroups. RESULTS:Risk of inadequate intake from food alone ranged from 0% to 87%, depending on the micronutrient and assessment methodology. When dietary supplements were included, some women were below the EAR for vitamin D (20-38%), vitamin E (17-22%), and magnesium (39-41%); some women were above the AI for vitamin K (63-75%), choline (7%), and potassium (37-53%); and some were above the UL for folic acid (32-51%), iron (39-40%), and zinc (19-20%). Highest risks for inadequate intakes were observed among participants with age 14-18 y (6 nutrients), non-White race or Hispanic ethnicity (10 nutrients), less than a high school education (9 nutrients), or obesity (9 nutrients). CONCLUSIONS:Improved diet quality is needed for most pregnant females. Even with dietary supplement use, >20% of participants were at risk of inadequate intake of ≥1 micronutrients, especially in some population subgroups. Pregnancy may be a window of opportunity to address disparities in micronutrient intake that could contribute to intergenerational health inequalities.
PMID: 34494118
ISSN: 1541-6100
CID: 5061252

Prenatal Exposure to Nonpersistent Chemical Mixtures and Fetal Growth: A Population-Based Study

van den Dries, Michiel A; Keil, Alexander P; Tiemeier, Henning; Pronk, Anjoeka; Spaan, Suzanne; Santos, Susana; Asimakopoulos, Alexandros G; Kannan, Kurunthachalam; Gaillard, Romy; Guxens, Mònica; Trasande, Leonardo; Jaddoe, Vincent W V; Ferguson, Kelly K
BACKGROUND:Prenatal exposure to mixtures of nonpersistent chemicals is universal. Most studies examining these chemicals in association with fetal growth have been restricted to single exposure models, ignoring their potentially cumulative impact. OBJECTIVE:We aimed to assess the association between prenatal exposure to a mixture of phthalates, bisphenols, and organophosphate (OP) pesticides and fetal measures of head circumference, femur length, and weight. METHODS: RESULTS: DISCUSSION/CONCLUSIONS:Higher exposure to a mixture of phthalates, bisphenols, and OP pesticides was associated with lower EFW in the midpregnancy period. In late pregnancy, these differences were similar but less pronounced. At birth, the only associations observed appeared when comparing individuals from Q1 and Q4. This finding suggests that even low levels of exposure may be sufficient to influence growth in early pregnancy, whereas higher levels may be necessary to affect birth weight. Joint exposure to nonpersistent chemicals may adversely impact fetal growth, and because these exposures are widespread, this impact could be substantial.
PMID: 34817287
ISSN: 1552-9924
CID: 5063642

Timing of Toenail Collection and Concentrations of Metals in Pancreatic Cancer. Evidence Against Disease Progression Bias

Pumarega, José; Camargo, Judit; Gasull, Magda; Olshan, Andrew F; Soliman, Amr; Chen, Yu; Richardson, David; Alguacil, Juan; Poole, Charles; Trasande, Leonardo; Porta, Miquel
Trace elements such as cadmium, arsenic, zinc or selenium increase or decrease risk of a wide range of human diseases. Their levels in toenails may provide a measure of mid-term intake of trace elements for studies in humans. However, in biologically and clinically aggressive diseases as pancreatic cancer, the progression of the disease could modify such concentrations and produce reverse causation bias. The aim was to analyze the influence of specific time intervals between several clinical events and the collection of toenails upon concentrations of trace elements in patients with pancreatic cancer. Subjects were 118 incident cases of pancreatic adenocarcinoma prospectively recruited in eastern Spain. Toenails were collected at cancer diagnosis, and soon thereafter interviews were conducted. Information on cancer signs and symptoms was obtained from medical records and patient interviews. Levels of 12 trace elements were determined in toenail samples by inductively coupled plasma mass spectrometry. General linear models adjusting for potential confounders were applied to analyze relations between log concentrations of trace elements and the time intervals, including the interval from first symptom of cancer to toenail collection (iST). Toenail concentrations of the 12 trace elements were weakly or not influenced by the progression of the disease or the diagnostic procedures. Concentrations of aluminum were slightly higher in subjects with a longer iST (age, sex and stage adjusted geometric means: 11.44 vs. 7.75 µg/g for iST > 120 days vs. ≤ 40 days). There was a weak inverse relation of iST with concentrations of zinc and selenium (maximum differences of about 20 and 0.08 µg/g, respectively). Conclusions: concentrations of the trace elements were weakly or not influenced by the development of the disease before toenail collection. Only concentrations of aluminum increased slightly with increasing iST, whereas levels of zinc and selenium decreased weakly. Even in an aggressive disease as pancreatic cancer, toenail concentrations of trace elements may provide a valid measure of mid-term intake of trace elements, unaffected by clinical events and disease progression.
PMID: 34722949
ISSN: 2451-9766
CID: 5037802

Associations of maternal bisphenol urine concentrations during pregnancy with neonatal metabolomic profiles

Blaauwendraad, Sophia M; Voerman, Ellis; Trasande, Leonardo; Kannan, Kurunthachalam; Santos, Susana; Ruijter, George J G; Sol, Chalana M; Marchioro, Linda; Shokry, Engy; Koletzko, Berthold; Jaddoe, Vincent W V; Gaillard, Romy
BACKGROUND:Fetal exposure to bisphenols is associated with altered fetal growth, adverse birth outcomes and childhood cardio-metabolic risk factors. Metabolomics may serve as a tool to identify the mechanisms underlying these associations. We examined the associations of maternal bisphenol urinary concentrations in pregnancy with neonatal metabolite profiles from cord blood. METHODS:In a population-based prospective cohort study among 225 mother-child pairs, maternal urinary bisphenol A, S and F concentrations in first, second and third trimester were measured. LC-MS/MS was used to determine neonatal concentrations of amino acids, non-esterified fatty acids (NEFA), phospholipids (PL), and carnitines in cord blood. RESULTS:No associations of maternal total bisphenol concentrations with neonatal metabolite profiles were present. Higher maternal average BPA concentrations were associated with higher neonatal mono-unsaturated alkyl-lysophosphatidylcholine concentrations, whereas higher maternal average BPS was associated with lower neonatal overall and saturated alkyl-lysophosphatidylcholine (p-values < 0.05).Trimester-specific analyses showed that higher maternal BPA, BPS and BPF were associated with alterations in neonatal NEFA, diacyl-phosphatidylcholines, acyl-alkyl-phosphatidylcholines, alkyl-lysophosphatidylcholine, sphingomyelines and acyl-carnitines, with the strongest effects for third trimester maternal bisphenol and neonatal diacyl-phosphatidylcholine, sphingomyeline and acyl-carnitine metabolites (p-values < 0.05). Associations were not explained by maternal socio-demographic and lifestyle characteristics or birth characteristics. DISCUSSION/CONCLUSIONS:Higher maternal bisphenol A, F and S concentrations in pregnancy are associated with alterations in neonatal metabolite profile, mainly in NEFA, PL and carnitines concentrations. These findings provide novel insight into potential mechanisms underlying associations of maternal bisphenol exposure during pregnancy with adverse offspring outcomes but need to be replicated among larger, diverse populations.
PMID: 34518915
ISSN: 1573-3890
CID: 4996582

Factors Associated With Changes in Pregnancy Intention Among Women Who Were Mothers of Young Children in New York City Following the COVID-19 Outbreak

Kahn, Linda G; Trasande, Leonardo; Liu, Mengling; Mehta-Lee, Shilpi S; Brubaker, Sara G; Jacobson, Melanie H
Importance:Early evidence shows a decrease in the number of US births during the COVID-19 pandemic, yet few studies have examined individual-level factors associated with pregnancy intention changes, especially among diverse study populations or in areas highly affected by COVID-19 in the US. Objective:To study changes in pregnancy intention following the outbreak of the COVID-19 pandemic and identify factors possibly associated with these changes. Design, Setting, and Participants:A cross-sectional, population-based study was conducted among women who were currently pregnant or had delivered a live infant and responded to a survey emailed to 2603 women (n = 1560). Women who were mothers of young children enrolled in the prospective New York University Children's Health and Environment Study birth cohort were included; women who were not currently pregnant or recently postpartum were excluded. Exposures:Demographic, COVID-19-related, stress-related, and financial/occupational factors were assessed via a survey administered from April 20 to August 31, 2020. Main Outcomes and Measures:Pregnancy intentions before the COVID-19 pandemic and change in pregnancy intentions following the outbreak. Results:Of the 2603 women who were sent the survey, 1560 (59.9%) who were currently pregnant or had delivered a live infant responded, and 1179 women (75.6%) answered the pregnancy intention questions. Mean (SD) age was 32.2 (5.6) years. Following the outbreak, 30 of 61 (49.2%) women who had been actively trying to become pregnant had ceased trying, 71 of 191 (37.2%) women who had been planning to become pregnant were no longer planning, and 42 of 927 (4.5%) women who were neither planning nor trying were newly considering pregnancy. Among those who ceased trying, fewer than half (13 [43.3%]) thought they would resume after the pandemic. Of those pre-COVID-19 planners/triers who stopped considering or attempting pregnancy, a greater proportion had lower educational levels, although the difference was not statistically significant on multivariable analysis (odds ratio [OR], 2.14; 95% CI, 0.92-4.96). The same was true for those with higher stress levels (OR, 1.09; 95% CI, 0.99-1.20) and those with greater financial insecurity (OR, 1.37; 95% CI, 0.97-1.92. Those who stopped considering or attempting pregnancy were more likely to respond to the questionnaire during the peak of the outbreak (OR, 2.04; 95% CI, 1.01-4.11). Of those pre-COVID-19 nonplanners/nontriers who reported newly thinking about becoming pregnant, a smaller proportion responded during the peak, although the finding was not statistically significant on multivariable analysis (OR, 0.52; 95% CI, 0.26-1.03). Likewise, fewer respondents who were financially insecure reported newly considering pregnancy, although the finding was not statistically significant (OR, 0.69; 95% CI, 0.46-1.03). They were significantly less likely to be of Hispanic ethnicity (OR, 0.27; 955 CI, 0.10-0.71) and more likely to have fewer children in the home (OR, 0.62; 95% CI, 0.40-0.98) or self-report a COVID-19 diagnosis (OR, 2.70; 95% CI, 1.31-5.55). Conclusions and Relevance:In this cross-sectional study of 1179 women who were mothers of young children in New York City, increased stress and financial insecurity owing to the COVID-19 pandemic paralleled a reduction in pregnancy intention in the early months of the pandemic, potentially exacerbating long-term decreases in the fertility rate.
PMID: 34524437
ISSN: 2574-3805
CID: 5012352