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BACKGROUND: Antidepressants are among the most commonly prescribed medications, but evidence on comparative weight change for specific first-line treatments is limited. OBJECTIVE: To compare weight change across common first-line antidepressant treatments by emulating a target trial. DESIGN: Observational cohort study over 24 months. SETTING: Electronic health record (EHR) data from 2010 to 2019 across 8 U.S. health systems. PARTICIPANTS: 183 118 patients. MEASUREMENTS: Prescription data determined initiation of treatment with sertraline, citalopram, escitalopram, fluoxetine, paroxetine, bupropion, duloxetine, or venlafaxine. The investigators estimated the population-level effects of initiating each treatment, relative to sertraline, on mean weight change (primary) and the probability of gaining at least 5% of baseline weight (secondary) 6 months after initiation. Inverse probability weighting of repeated outcome marginal structural models was used to account for baseline confounding and informative outcome measurement. In secondary analyses, the effects of initiating and adhering to each treatment protocol were estimated. RESULTS: Compared with that for sertraline, estimated 6-month weight gain was higher for escitalopram (difference, 0.41 kg [95% CI, 0.31 to 0.52 kg]), paroxetine (difference, 0.37 kg [CI, 0.20 to 0.54 kg]), duloxetine (difference, 0.34 kg [CI, 0.22 to 0.44 kg]), venlafaxine (difference, 0.17 kg [CI, 0.03 to 0.31 kg]), and citalopram (difference, 0.12 kg [CI, 0.02 to 0.23 kg]); similar for fluoxetine (difference, -0.07 kg [CI, -0.19 to 0.04 kg]); and lower for bupropion (difference, -0.22 kg [CI, -0.33 to -0.12 kg]). Escitalopram, paroxetine, and duloxetine were associated with 10% to 15% higher risk for gaining at least 5% of baseline weight, whereas bupropion was associated with 15% reduced risk. When the effects of initiation and adherence were estimated, associations were stronger but had wider CIs. Six-month adherence ranged from 28% (duloxetine) to 41% (bupropion). LIMITATION: No data on medication dispensing, low medication adherence, incomplete data on adherence, and incomplete data on weight measures across time points. CONCLUSION: Small differences in mean weight change were found between 8 first-line antidepressants, with bupropion consistently showing the least weight gain, although adherence to medications over follow-up was low. Clinicians could consider potential weight gain when initiating antidepressant treatment. PRIMARY FUNDING SOURCE: National Institutes of Health.
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Antidepresivos , Aumento de Peso , Humanos , Antidepresivos/uso terapéutico , Antidepresivos/efectos adversos , Femenino , Masculino , Aumento de Peso/efectos de los fármacos , Persona de Mediana Edad , Adulto , Bupropión/uso terapéutico , Bupropión/efectos adversos , Citalopram/uso terapéutico , Citalopram/efectos adversos , Clorhidrato de Duloxetina/uso terapéutico , Clorhidrato de Duloxetina/efectos adversos , AncianoRESUMEN
BACKGROUND: Hypertensive disorders of pregnancy (HDP) such as preeclampsia and gestational hypertension are major contributors to maternal and child morbidity and mortality. Previous studies have reported associations with selected metals and vitamins but are limited in sample size and non-prospective study designs. We evaluated prospective associations of metal mixtures with HDP and tested interactions by vitamins. STUDY DESIGN: We measured first trimester (median = 10.1 weeks) concentrations of essential (copper, magnesium, manganese, selenium, zinc) and nonessential (arsenic, barium, cadmium, cesium, mercury, lead) metals in red blood cells (n = 1,386) and vitamins (B12 and folate) in plasma (n = 924) in Project Viva, a pre-birth US cohort. We collected diagnosis of HDP by reviewing medical records. We used multinomial logistic regression and Bayesian Kernel Machine Regression to estimate individual and joint associations of metals with HDP and interactions by vitamins, after adjusting for key covariates. RESULTS: The majority of participants were non-Hispanic white (72.5 %), never smokers (68.5 %) with a mean (SD) age of 32.3 (4.6) years. Fifty-two (3.8 %) developed preeclampsia and 94 (6.8 %) gestational hypertension. A doubling in first trimester erythrocyte copper was associated with 78 % lower odds of preeclampsia (OR=0.22, 95 % confidence interval: 0.08, 0.60). We also observed significant associations between higher erythrocyte total arsenic and lower odds of preeclampsia (OR=0.80, 95 % CI: 0.66, 0.97) and higher vitamin B12 and increased odds of gestational hypertension (OR=1.79, 95 % CI: 1.09, 2.96), but associations were attenuated after adjustment for dietary factors. Lower levels of the overall metal mixture and essential metal mixture were associated with higher odds of preeclampsia. We found no evidence of interactions by prenatal vitamins or between metals. CONCLUSION: Lower levels of a first-trimester essential metal mixture were associated with an increased risk of preeclampsia, primarily driven by copper. No associations were observed between other metals and HDP after adjustment for confounders and diet.
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Hipertensión Inducida en el Embarazo , Primer Trimestre del Embarazo , Humanos , Femenino , Embarazo , Primer Trimestre del Embarazo/sangre , Adulto , Hipertensión Inducida en el Embarazo/epidemiología , Hipertensión Inducida en el Embarazo/sangre , Vitaminas/sangre , Metales/sangre , Estudios Prospectivos , Estudios de Cohortes , Exposición Materna/estadística & datos numéricosRESUMEN
BACKGROUND: Evidence suggests that prenatal per- and polyfluoroalkyl substances (PFAS) and metals, two classes of chemicals found ubiquitously in human populations, influence immune system development and response. OBJECTIVE: We evaluated whether first trimester blood PFAS and metals were associated with antigen- or mitogen-stimulated cord blood lymphocyte proliferation and cytokine secretion. METHODS: We measured six PFAS, as well as six nonessential and four essential metals, in first trimester blood from participants in the longitudinal pre-birth Project Viva cohort, recruited between 1999 and 2000 in eastern Massachusetts. We measured antigen- or mitogen-stimulated cord blood mononuclear cell proliferation responses (n = 269-314) and cytokine secretion (n = 217-302). We used covariate-adjusted least absolute shrinkage and selection operator (LASSO) for variable selection and multivariable regression to estimate associations with the immune markers. RESULTS: Each ng/mL of MeFOSAA was associated with a 3.6% (1.4, 5.8) higher lymphocyte proliferation response after stimulation with egg antigen, as well as 0.8 (0.7, 1.0) reduced odds of having IFN-γ detected in response to dust mite. Each ng/g increment of cesium was associated with 27.8% (-45.1, -4.9) lower IL-10 levels in response to dust mite. Each ng/g increment of mercury was associated with 12.0% (1.3, 23.8) higher IL-13 levels in response to mitogen PHA. Each ng/g increment of selenium and zinc was associated with 0.2% (0.01, 0.4) and 0.01% (0.002, 0.02) higher TNF-α in response to mitogen PHA, respectively. CONCLUSIONS: Prenatal metals and PFAS influence cord blood lymphocyte proliferation and cytokine secretion in ways that may increase risk for atopic disease in childhood.
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BACKGROUND: Limited access to healthy foods, resulting from residence in neighborhoods with low-food access or from household food insecurity, is a public health concern. Contributions of these measures during pregnancy to birth outcomes remain understudied. OBJECTIVES: We examined associations between neighborhood food access and individual food insecurity during pregnancy with birth outcomes. METHODS: We used data from 53 cohorts participating in the nationwide Environmental Influences on Child Health Outcomes-Wide Cohort Study. Participant inclusion required a geocoded residential address or response to a food insecurity question during pregnancy and information on birth outcomes. Exposures include low-income-low-food-access (LILA, where the nearest supermarket is >0.5 miles for urban or >10 miles for rural areas) or low-income-low-vehicle-access (LILV, where few households have a vehicle and >0.5 miles from the nearest supermarket) neighborhoods and individual food insecurity. Mixed-effects models estimated associations with birth outcomes, adjusting for socioeconomic and pregnancy characteristics. RESULTS: Among 22,206 pregnant participants (mean age 30.4 y) with neighborhood food access data, 24.1% resided in LILA neighborhoods and 13.6% in LILV neighborhoods. Of 1630 pregnant participants with individual-level food insecurity data (mean age 29.7 y), 8.0% experienced food insecurity. Residence in LILA (compared with non-LILA) neighborhoods was associated with lower birth weight [ß -44.3 g; 95% confidence interval (CI): -62.9, -25.6], lower birth weight-for-gestational-age z-score (-0.09 SD units; -0.12, -0.05), higher odds of small-for-gestational-age [odds ratio (OR) 1.15; 95% CI: 1.00, 1.33], and lower odds of large-for-gestational-age (0.85; 95% CI: 0.77, 0.94). Similar findings were observed for residence in LILV neighborhoods. No associations of individual food insecurity with birth outcomes were observed. CONCLUSIONS: Residence in LILA or LILV neighborhoods during pregnancy is associated with adverse birth outcomes. These findings highlight the need for future studies examining whether investing in neighborhood resources to improve food access during pregnancy would promote equitable birth outcomes.
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Inseguridad Alimentaria , Abastecimiento de Alimentos , Resultado del Embarazo , Humanos , Femenino , Embarazo , Estudios de Cohortes , Adulto , Abastecimiento de Alimentos/estadística & datos numéricos , Recién Nacido , Características del Vecindario , Características de la Residencia , Pobreza , Adulto JovenRESUMEN
BACKGROUND: Relatively little is known about the immediate and prospective neurodevelopmental impacts of joint exposure to multiple metals (i.e., metal mixtures) in early childhood. OBJECTIVES: To estimate associations of early childhood (â¼3 years of age) blood metal concentrations with cognitive test scores at early and mid-childhood (â¼8 years of age). METHODS: We studied children from the Project Viva cohort. We measured erythrocyte concentrations of seven essential (Co, Cu, Mg, Mn, Mo, Se, and Zn) and eight non-essential metals (As, Ba, Cd, Cs, Hg, Pb, Sn, and Sr) in early childhood blood samples. Trained research assistants administered cognitive tests assessing vocabulary, visual-motor ability, memory, and general intelligence (standard deviations: â¼10 points), in early and mid-childhood. We employed multivariable linear regression to examine associations of individual metals with test scores adjusting for confounders, other concurrently measured metals, and first-trimester maternal blood metals. We also estimated joint associations and explored interaction between metals in mixture analyses. RESULTS: We analyzed 349 children (median whole blood Pb â¼1 µg/dL). In cross-sectional analyses, each doubling of Pb was associated with lower visual-motor function (mean difference: -2.43 points, 95% confidence interval (CI): -4.01, -0.86) and receptive vocabulary, i.e., words understood (-1.45 points, 95% CI: -3.26, 0.36). Associations of Pb with mid-childhood cognition were weaker and less precise by comparison. Mg was positively associated with cognition in cross-sectional but not prospective analyses, and cross-sectional associations were attenuated in a sensitivity analysis removing adjustment for concurrent metals. We did not observe joint associations nor interactions. DISCUSSION: In this cohort with low blood Pb levels, increased blood Pb was robustly associated with lower cognitive ability in cross-sectional analyses, even after adjustment for prenatal Pb exposure, and regardless of adjustment for metal co-exposures. However, associations with mid-childhood cognition were attenuated and imprecise, suggesting some buffering of Pb neurotoxicity in early life. WHAT THIS STUDY ADDS: Relatively few studies have comprehensively separated the effects of neurotoxic metals such as lead (Pb) from pre- and postnatal co-occurring metals, nor examined persistence of associations across childhood. In a cohort of middle-class children, we found higher early childhood (â¼3 y) blood Pb was associated with lower scores on cognitive tests, independent of other metals and prenatal blood Pb. However, early childhood Pb was only weakly associated with cognition in mid-childhood (â¼8 y). Our results suggest the effects of low-level Pb exposure may attenuate over time in some populations, implying the presence of factors that may buffer Pb neurotoxicity in early life.
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Plomo , Mercurio , Embarazo , Femenino , Humanos , Preescolar , Niño , Estudios Transversales , Plomo/toxicidad , Cognición , Pruebas NeuropsicológicasRESUMEN
This cohort study assesses the association between 4 infant feeding practices and concentrations of 8 nonessential and 7 essential metals in red blood cells.
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Fenómenos Fisiológicos Nutricionales del Lactante , Metales , Humanos , Lactante , Metales/sangreRESUMEN
BACKGROUND: The developing fetal brain is sensitive to many environmental exposures. However, the independent and joint effects of prenatal exposure to metals and micronutrients on child cognition are not well understood. OBJECTIVES: Our aim was to evaluate associations of first-trimester (â¼10 wk) maternal erythrocyte concentrations of mixtures of nonessential and essential metals and micronutrients with early (â¼3 y) and mid-childhood (â¼8 y) cognitive test scores in Project Viva, a prebirth cohort in Boston, Massachusetts, USA. METHODS: We measured concentrations of five essential metals (Cu, Mg, Mn, Se, Zn) and two micronutrients (vitamin B12 and folate), together termed the "nutrient mixture," as well as six nonessential metals (As, Ba, Cd, Cs, Hg, Pb), together termed the "neurotoxic mixture," in first-trimester (â¼10 wk) maternal erythrocytes (metals) or plasma (micronutrients). We assessed visual-motor function and receptive vocabulary in early childhood (â¼3 y), and visual-motor function, visual memory, and fluid and crystallized intelligence in mid-childhood (â¼8 y). We employed adjusted quantile g-computation and linear regression to estimate mixture and individual component associations, respectively. RESULTS: Analyses included 900 mother-child pairs (74% college graduates; 52% male children). In mixture analyses, a quartile increase in the nutrient mixture was associated with a mean difference in early childhood receptive vocabulary score of 1.58 points [95% confidence interval (CI): 0.06, 3.10], driven by Zn and Se. A quartile increase in the neurotoxic mixture was associated with a mean difference in mid-childhood visual-motor score of -3.01 points (95% CI: -5.55, -0.47), driven by Ba and Cs. Linear regressions supported quantile g-computation findings for mixture component contributions. DISCUSSION: Maternal circulating concentrations of several essential (Zn and Se) and nonessential (Ba and Cs) metals were associated with some domains of child cognition. In this folate-replete cohort, first-trimester circulating concentrations of known neurotoxic metals, such as Pb, were not associated with child cognition. https://doi.org/10.1289/EHP12016.
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Micronutrientes , Efectos Tardíos de la Exposición Prenatal , Embarazo , Femenino , Humanos , Masculino , Preescolar , Niño , Micronutrientes/farmacología , Plomo , Efectos Tardíos de la Exposición Prenatal/epidemiología , Cognición , Ácido Fólico/farmacologíaRESUMEN
In this work, we propose the use of molecular emission of calcium fluoride (CaF) by laser induced breakdown spectroscopy (LIBS) to obtain quantitative fluoride distribution images of teeth. LIBS has proved to be an efficient technique to detect low amounts of fluoride in solids, and human teeth have the advantage being a matrix rich in calcium. We used new calibration material from sintered hydroxyapatite pellets doped with fluoride to determine the optimized LIBS conditions of argon flow at 1 L min-1 and using the green emission bands of CaF in 530 nm, and obtained a calibration curve between 0 and 400 µg g-1, and LOD of 18 µg g-1. This methodology was applied within a rat model of fluoride exposure and showed increasing tooth-fluoride with increased exposure dose. To demonstrate applicability of this method in human teeth, we quantified fluoride distribution in teeth from three children from non-fluorinated and fluorinated water regions. Samples from children living in fluoridated water regions showed higher fluoride concentrations in dentine formed after birth, compared to a child from a non-fluoridated region. Teeth have been used as biomarkers for environmental exposure and this new method opens the opportunity in epidemiology research to study critical windows of early life exposure to fluoride as well.
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BACKGROUND: Epidemiologic evidence linking prenatal exposure to per- and polyfluoroalkyl substances (PFAS) with altered neurodevelopment is inconclusive, and few large studies have focused on autism-related outcomes. We investigated whether blood concentrations of PFAS in pregnancy are associated with child autism-related outcomes. METHODS: We included 10 cohorts from the National Institutes of Health (NIH)-funded Environmental influences on Child Health Outcomes (ECHO) program (n = 1,429). We measured 14 PFAS analytes in maternal blood collected during pregnancy; eight analytes met detection criteria for analysis. We assessed quantitative autism-related traits in children via parent report on the Social Responsiveness Scale (SRS). In multivariable linear models, we examined relationships of each PFAS (natural log-transformed) with SRS scores. We further modeled PFAS as a complex mixture using Bayesian methods and examined modification of these relationships by child sex. RESULTS: Most PFAS in maternal blood were not associated with child SRS T-scores. Perfluorononanoic acid (PFNA) showed the strongest and most consistent association: each 1-unit increase in ln-transformed PFNA was associated with greater autism-related traits (adjusted ß [95% confidence interval (CI)] = 1.5 [-0.1, 3.0]). The summed mixture, which included six PFAS detected in >70% of participants, was not associated with SRS T-scores (adjusted ß [95% highest posterior density interval] = 0.7 [-1.4, 3.0]). We did not observe consistent evidence of sex differences. CONCLUSIONS: Prenatal blood concentrations of PFNA may be associated with modest increases in child autism-related traits. Future work should continue to examine the relationship between exposures to both legacy and emerging PFAS and additional dimensional, quantitative measures of childhood autism-related outcomes.
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Ácidos Alcanesulfónicos , Trastorno Autístico , Contaminantes Ambientales , Fluorocarburos , Efectos Tardíos de la Exposición Prenatal , Niño , Embarazo , Humanos , Masculino , Femenino , Efectos Tardíos de la Exposición Prenatal/epidemiología , Trastorno Autístico/epidemiología , Teorema de BayesRESUMEN
Some trace elements are established nephrotoxicants, yet their associations with kidney function remain understudied in the context of pregnancy, a time of substantial change in kidney physiology and function. We aimed to estimate the individual and joint associations of trace element mixtures with maternal kidney function during the 1st trimester of pregnancy (mean 9.7 gestational weeks). 1040 women from Project Viva contributed blood samples which were assessed for erythrocyte non-essential [arsenic (As), cadmium (Cd), cesium (Cs), mercury (Hg), lead (Pb)] and essential [barium (Ba), magnesium (Mg), manganese (Mn), selenium (Se), and Zinc (Zn)] trace elements, and plasma creatinine for kidney function. We estimated glomerular filtration rate using the Chronic Kidney Disease Epidemiology Collaboration (eGFRCKD-EPI) equation without race-adjustment factors. We examined associations of eGFRCKD-EPI with individual trace elements using multivariable linear regression and their mixtures using quantile-based g-computation, adjusting for sociodemographics, pregnancy characteristics, and diet. Participants in our study were predominantly White (75%), college graduates (72%), and had household income >$70,000/year (63%). After adjusting for covariates, higher Pb (ß -3.51 ml/min/1.73 m2; 95% CI -5.83, -1.18) concentrations were associated with lower eGFRCKD-EPI, while higher Mg (ß 10.53 ml/min/1.73 m2; 95% CI 5.35, 15.71), Se (ß 5.56 ml/min/1.73 m2; 95% CI 0.82, 10.31), and Zn (ß 5.88 ml/min/1.73 m2; 95% CI 0.51, 11.26) concentrations were associated with higher eGFRCKD-EPI. In mixture analyses, higher non-essential trace elements mixture concentration was associated with reduced eGFRCKD-EPI (Ψ -1.03 ml/min/1.73 m2; 95% CI: 1.92, -0.14). Conversely, higher essential trace elements mixture concentration was associated with higher eGFR (Ψ 1.42; 95% CI: 0.48, 2.37). Exposure to trace elements in early pregnancy may influence women's kidney function although reverse causation cannot be eliminated in this cross-sectional analysis. These findings have important implications for long-term cardiovascular and postpartum kidney health that warrant additional studies.
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Mercurio , Insuficiencia Renal Crónica , Selenio , Oligoelementos , Embarazo , Femenino , Humanos , Estudios Transversales , Plomo , RiñónRESUMEN
BACKGROUND: Prenatal nonessential metals may contribute to postnatal adiposity, whereas essential metals may have metabolic benefits. We evaluated joint and individual associations between prenatal metals and childhood adiposity. METHODS: We measured concentrations of six nonessential (arsenic, barium, cadmium, cesium, lead, and mercury) and four essential (magnesium, manganese, selenium, and zinc) metals in first trimester maternal blood from a prebirth cohort. We collected anthropometric measures in early childhood, mid-childhood, and early adolescence including subscapular+tricep skinfold thickness (mm) (N = 715-859), waist circumference (cm) (N = 717-882), and body mass index (BMI) (z-score) (N = 716-875). We measured adiposity in mid-childhood and early adolescence using bone densitometry total- and trunk- fat mass index (kg/m 2 ) (N = 511-599). We estimated associations using adjusted quantile g-computation and linear regression. RESULTS: The nonessential metal mixture was associated with higher total (ß = 0.07, 95% CI = 0.01, 0.12) and trunk fat mass index (ß = 0.12, CI = 0.02, 0.22), waist circumference (ß = 0.01, CI = 0.00, 0.01), and BMI (ß = 0.24, CI = 0.07, 0.41) in mid-childhood, and total fat mass index (ß = 0.07, CI = 0.01, 0.14), and BMI (ß = 0.19, CI = 0.02, 0.37) in early adolescence. The essential metal mixture was associated with lower early adolescence total-(ß = -0.11, CI = -0.17, -0.04) and trunk- fat mass index (ß = -0.13, CI = -0.21, -0.05), subscapular+tricep skinfold thickness (ß = -0.02, CI = -0.03, -0.00), waist circumference (ß = -0.003, CI = -0.01, -0.00), and BMI (ß = -0.16, CI = -0.28, -0.04). Cadmium and cesium were individually associated with childhood adiposity at different timepoints. CONCLUSIONS: Prenatal first-trimester essential metals were associated with lower childhood adiposity, whereas nonessential metals were associated with higher adiposity into adolescence.
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Adiposidad , Obesidad Infantil , Preescolar , Adolescente , Femenino , Embarazo , Humanos , Niño , Primer Trimestre del Embarazo , Cadmio , Tamaño Corporal , Metales , Obesidad Infantil/epidemiologíaRESUMEN
BACKGROUND: Mood disorders are common during and after pregnancy, and environmental metals may contribute to increased risk. Antepartum metal exposures have not been well characterized in relation to maternal depression. We evaluated the extent to which early pregnancy erythrocyte concentrations of essential and non-essential metals were prospectively associated with antepartum and postpartum depressive symptoms. METHODS: Participants were 1226 women in Project Viva, a longitudinal cohort recruited during pregnancy (1999-2002). We measured concentrations of 11 metals in maternal first trimester erythrocytes (arsenic, barium, cadmium, cesium, copper, mercury, magnesium, manganese, lead, selenium, zinc). Using the Edinburgh Postnatal Depression Scale (EPDS), we assessed elevated depressive symptoms (≥13; 0-30 scale) at mid-pregnancy and at 6 and 12 months postpartum. We applied latent class mixed modeling to identify symptom trajectories. Adjusting for maternal sociodemographics and co-exposures, we examined associations between the metal mixture and depressive symptoms using logistic (for EPDS≥13)/multinomial (for symptom trajectories) regression and quantile g-computation. RESULTS: In this cohort of moderately high socioeconomic status participants (e.g., 72 % college graduate), low-level metal concentrations were weakly to moderately correlated (Spearman: -0.24 to 0.59); the prevalence of depressive symptoms ranged from 9 % (mid-pregnancy) to 6 % (12 months postpartum); and three trajectories (stable low; elevated mid-pregnancy, then decreasing; moderate mid-pregnancy, then increasing) best fit the EPDS data. The early pregnancy erythrocyte metal mixture was not associated with maternal depressive symptoms in logistic, multinomial, or mixture models. For individual metals, most confidence intervals (CI) included the null. There was weak evidence that arsenic, lead, and selenium were moderately associated with elevated odds of depressive symptoms and/or trajectories. However, the odds ratios (95 % CI) per doubling of these three metals were imprecise [e.g., arsenic: 1.13 (0.94, 1.40) for EPDS≥13 at six months postpartum; lead: 1.19 (0.80, 1.77) for EPDS≥13 at mid-pregnancy; selenium: 2.35 (0.84, 6.57) for elevated mid-pregnancy, then decreasing versus stable low trajectory]. DISCUSSION: We did not observe strong, consistent evidence of associations between early pregnancy erythrocyte metal concentrations and subsequent maternal antepartum and postpartum depressive symptoms.
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Arsénico , Depresión Posparto , Selenio , Embarazo , Femenino , Humanos , Depresión/diagnóstico , Depresión/epidemiología , Depresión/etiología , Depresión Posparto/diagnóstico , Depresión Posparto/epidemiología , Periodo PospartoRESUMEN
Prenatal antidepressant exposure has been associated with increased risk for neurodevelopmental disorders in childhood, including autism spectrum disorder (ASD). The current study utilized multi-cohort data from the Environmental influences on Child Health Outcomes (ECHO) program (N = 3129) to test for this association, and determine whether the association remained after adjusting for maternal prenatal depression and other potential confounders. Antidepressants and a subset of selective serotonin reuptake inhibitors (SSRIs) were examined in relation to binary (e.g., diagnostic) and continuous measures of ASD and ASD related traits (e.g., social difficulties, behavior problems) in children 1.5 to 12 years of age. Child sex was tested as an effect modifier. While prenatal antidepressant exposure was associated with ASD related traits in univariate analyses, these associations were statistically non-significant in models that adjusted for prenatal maternal depression and other maternal and child characteristics. Sex assigned at birth was not an effect modifier for the prenatal antidepressant and child ASD relationship. Overall, we found no association between prenatal antidepressant exposures and ASD diagnoses or traits. Discontinuation of antidepressants in pregnancy does not appear to be warranted on the basis of increased risk for offspring ASD.
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Trastorno del Espectro Autista , Efectos Tardíos de la Exposición Prenatal , Niño , Embarazo , Femenino , Humanos , Estudios Retrospectivos , Estudios de Cohortes , Trastorno del Espectro Autista/inducido químicamente , Trastorno del Espectro Autista/epidemiología , Trastorno del Espectro Autista/tratamiento farmacológico , Efectos Tardíos de la Exposición Prenatal/epidemiología , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Efectos Tardíos de la Exposición Prenatal/tratamiento farmacológico , Antidepresivos/efectos adversosRESUMEN
Background: Nonessential metals have endocrine disrupting properties, interfere with cellular processes, generate reactive oxygen and deplete antioxidants, while essential metals and vitamins act as antioxidants. The extent to which prenatal metals and vitamins are associated with cord blood hormones involved in maternal and fetal metabolic and growth processes is unknown. Methods: We measured six nonessential (arsenic, barium, cadmium, cesium, lead, mercury) and four essential (magnesium, manganese, selenium, zinc) metals and trace elements, and two vitamins (B12 and folate) in first trimester blood from participants in the longitudinal pre-birth Project Viva cohort, who were recruited between 1999-2002 in eastern Massachusetts. We measured adiponectin, C-peptide, IGF-1, IGF-2, IGFBP-3, insulin, and leptin concentrations in cord blood (~n=695). We used covariate-adjusted quantile g-computation for mixtures and linear regression for individual exposures to estimate associations with cord blood peptide hormones. Results: The essential metal mixture (magnesium, manganese, selenium, zinc) was associated with higher IGF-1 (ß=3.20 ng/ml per quartile, 95% CI: 0.39, 6.01), IGF-2 (ß=10.93 ng/ml, 95% CI: 0.08, 21.79), and leptin (ß=1.03 ng/ml, 95% CI: 0.25, 1.80). Magnesium was associated with higher leptin (ß=2.90 ng/ml, 95% CI: 0.89, 4.91), while B12 was associated with lower adiponectin, IGF-2, and leptin, but higher C-peptide. Other individual nonessential metals were associated with cord blood hormones. Conclusions: Our findings suggest that some prenatal metals and vitamins are associated with cord blood hormones, which may influence growth and development.
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Objective: To demonstrate the utility of growthcleanr, an anthropometric data cleaning method designed for electronic health records (EHR). Materials and Methods: We used all available pediatric and adult height and weight data from an ongoing observational study that includes EHR data from 15 healthcare systems and applied growthcleanr to identify outliers and errors and compared its performance in pediatric data with 2 other pediatric data cleaning methods: (1) conditional percentile (cp) and (2) PaEdiatric ANthropometric measurement Outlier Flagging pipeline (peanof). Results: 687 226 children (<20 years) and 3 267 293 adults contributed 71 246 369 weight and 51 525 487 height measurements. growthcleanr flagged 18% of pediatric and 12% of adult measurements for exclusion, mostly as carried-forward measures for pediatric data and duplicates for adult and pediatric data. After removing the flagged measurements, 0.5% and 0.6% of the pediatric heights and weights and 0.3% and 1.4% of the adult heights and weights, respectively, were biologically implausible according to the CDC and other established cut points. Compared with other pediatric cleaning methods, growthcleanr flagged the most measurements for exclusion; however, it did not flag some more extreme measurements. The prevalence of severe pediatric obesity was 9.0%, 9.2%, and 8.0% after cleaning by growthcleanr, cp, and peanof, respectively. Conclusion: growthcleanr is useful for cleaning pediatric and adult height and weight data. It is the only method with the ability to clean adult data and identify carried-forward and duplicates, which are prevalent in EHR. Findings of this study can be used to improve the growthcleanr algorithm.
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BACKGROUND: Lactation has long term effects on maternal health, but the relationship between lactation and long-term handgrip strength, a marker of musculoskeletal function and healthy aging, has not been explored. OBJECTIVE: Examine the relationship between total lifetime breastfeeding duration (BFD) and midlife handgrip strength. METHODS: We measured handgrip strength as a marker of overall strength among 631 women in the Project Viva cohort. At the same visit, women reported their BFD for each birth, and we derived total lifetime BFD. We used multivariable linear regression models to estimate associations of lifetime BFD in months with midlife handgrip strength in kilograms, adjusted for race/ethnicity, education, marital status, household income, age at first pregnancy and age at handgrip strength assessment. RESULTS: Mean (standard deviation) age was 50.7 (5.1) years, lifetime BFD was 21.6 (19.5) months, and handgrip strength was 28.0 kg (6.0) in the dominant and 26.0 kg (5.6) in the non-dominant hand. In fully adjusted models, each 3-month increment in lifetime BFD was associated with 0.10 kg (95% CI 0.02, 0.18) higher handgrip strength for the dominant hand and 0.10 kg (95% CI 0.03, 0.18) for the nondominant hand. Results were similar in models examining mean BFD per pregnancy rather than total BFD. There was no evidence of effect modification by race/ethnicity. CONCLUSIONS: Our study suggests that there is a small beneficial effect of lifetime BFD on handgrip strength. Future studies can explore mechanisms by which BFD affects body composition and associations with other outcomes related to lean mass such as sarcopenia.
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Fuerza de la Mano , Sarcopenia , Composición Corporal , Lactancia Materna , Estudios de Cohortes , Femenino , Humanos , Persona de Mediana EdadRESUMEN
BACKGROUND: Prior studies of early antibiotic use and growth have shown mixed results, primarily on cross-sectional outcomes. This study examined the effect of oral antibiotics before age 24 months on growth trajectory at age 2-5 years. METHODS: We captured oral antibiotic prescriptions and anthropometrics from electronic health records through PCORnet, for children with ≥1 height and weight at 0-12 months of age, ≥1 at 12-30 months, and ≥2 between 25 and 72 months. Prescriptions were grouped into episodes by time and by antimicrobial spectrum. Longitudinal rate regression was used to assess differences in growth rate from 25 to 72 months of age. Models were adjusted for sex, race/ethnicity, steroid use, diagnosed asthma, complex chronic conditions, and infections. RESULTS: 430,376 children from 29 health U.S. systems were included, with 58% receiving antibiotics before 24 months. Exposure to any antibiotic was associated with an average 0.7% (95% CI 0.5, 0.9, p < 0.0001) greater rate of weight gain, corresponding to 0.05 kg additional weight. The estimated effect was slightly greater for narrow-spectrum (0.8% [0.6, 1.1]) than broad-spectrum (0.6% [0.3, 0.8], p < 0.0001) drugs. There was a small dose response relationship between the number of antibiotic episodes and weight gain. CONCLUSION: Oral antibiotic use prior to 24 months of age was associated with very small changes in average growth rate at ages 2-5 years. The small effect size is unlikely to affect individual prescribing decisions, though it may reflect a biologic effect that can combine with others.
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Antibacterianos , Estatura , Antibacterianos/uso terapéutico , Niño , Preescolar , Estudios Transversales , Humanos , Lactante , Prescripciones , Aumento de PesoRESUMEN
BACKGROUND: Metal exposure during pregnancy influences maternal and child health. Oxidative stress and inflammation may mediate adverse effects of heavy metals, whereas essential metals may act as antioxidants. Mitochondrial DNA is a prime target for metal-induced oxidative damage. Telomere dysfunction is attributed to imbalances between reactive oxidant species and antioxidants. OBJECTIVES: We evaluated individual and joint associations of prenatal metals with mitochondrial DNA copy number (mtDNAcn) and telomere length (TL) in maternal and cord blood as biomarkers of inflammation and oxidative stress. METHODS: We measured six nonessential metals (arsenic, barium, cadmium, cesium, lead, mercury) and four essential metals (magnesium, manganese, selenium, zinc) in first-trimester maternal red blood cells in Project Viva, a U.S. prebirth cohort. We measured relative mtDNAcn (n=898) and TL (n=893) in second-trimester maternal blood and mtDNAcn (n=419) and TL (n=408) in cord blood. We used multivariable linear regression and quantile g-computation to estimate associations between prenatal metals and the biomarkers. We used generalized additive models and Bayesian kernel machine regression to examine nonlinearity and interactions. RESULTS: A 2-fold increase in maternal magnesium was associated with lower maternal [ß=-0.07, 95% confidence interval (CI): -0.10, -0.01] and cord blood (ß=-0.08, 95% CI: -0.20, -0.01) mtDNAcn. Lead was associated with higher maternal mtDNAcn (ß=0.04, 95% CI: 0.01, 0.06). Selenium was associated with longer cord blood TL (ß=0.30, 95% CI: 0.01 0.50). An association was observed between the nonessential metal mixture and higher maternal mtDNAcn (ß=0.04, 95% CI: 0.01, 0.07). There was a nonlinear relationship between cord blood mtDNAcn and magnesium; maternal mtDNAcn and barium, lead, and mercury; and maternal TL and barium. DISCUSSION: Maternal exposure to metals such as lead, magnesium, and selenium was associated with mtDNAcn and TL in maternal second trimester and cord blood. Future work will evaluate whether these biomarkers are associated with child health. https://doi.org/10.1289/EHP9294.
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Sangre Fetal , Metales Pesados , Teorema de Bayes , Niño , Variaciones en el Número de Copia de ADN , ADN Mitocondrial/genética , Femenino , Humanos , Mitocondrias , Embarazo , TelómeroRESUMEN
BACKGROUND: Understanding the temporal trends and change of concentrations of per- and polyfluoroalkyl substances (PFAS) is important to evaluate the health impact of PFAS at both the individual- and population-level, however, limited information is available for pre-diabetic adults in the U.S. OBJECTIVES: Determine trends and rate of change of plasma PFAS concentrations in overweight or obese U.S. adults and evaluate variation by sex, race/ethnicity, and age. METHODS: We described temporal trends of plasma PFAS concentrations using samples collected in 1996-1998, 1999-2001, and 2011-2012 from 957 pre-diabetic adults enrolled in the Diabetes Prevention Program (DPP) trial and Outcomes Study (DPPOS) and compared to serum concentrations from the National Health and Nutrition Examination Survey (NHANES 1999-2000, 2003-2016, adults with BMI ≥ 24 kg/m2). We examined associations between participants' characteristics and PFAS concentrations and estimated the rate of change using repeated measures in DPP/DPPOS assuming a first-order elimination model. RESULTS: Longitudinal measures of PFAS concentrations in DPP/DPPOS individuals were comparable to NHANES cross-sectional populational means. Plasma concentrations of perfluorooctanesulfonic acid (PFOS), perfluorooctanoic acid, perfluorohexanesulfonic acid (PFHxS), N-ethyl-perfluorooctane sulfonamido acetic acid (EtFOSAA), and N-methylperfluorooctane sulfonamido acetic acid (MeFOSAA) started to decline after the year 2000 and concentrations of perfluorononanoic acid (PFNA) increased after 2000 and, for NHANES, decreased after 2012. We consistently observed higher PFOS, PFHxS and PFNA among male, compared to female, and higher PFOS and PFNA among Black, compared to white, participants. The estimated time for concentrations to decrease by half ranged from 3.39 years for EtFOSAA to 17.56 years for PFHxS. DISCUSSION: We observed a downward temporal trend in plasma PFOS concentrations that was consistent with the timing for U.S. manufacturers' phaseout. Male and Black participants consistently showed higher PFOS and PFNA than female and white participants, likely due to differences in exposure patterns, metabolism or elimination kinetics.
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Ácidos Alcanesulfónicos , Diabetes Mellitus Tipo 2 , Contaminantes Ambientales , Fluorocarburos , Adulto , Estudios Transversales , Femenino , Humanos , Masculino , Encuestas Nutricionales , Obesidad/prevención & control , Sobrepeso , Estados UnidosRESUMEN
Importance: Past studies have showed associations between antibiotic exposure and child weight outcomes. Few, however, have documented alterations to body mass index (BMI) (calculated as weight in kilograms divided by height in meters squared) trajectory milestone patterns during childhood after early-life antibiotic exposure. Objective: To examine the association of antibiotic use during the first 48 months of life with BMI trajectory milestones during childhood in a large cohort of children. Design, Setting, and Participants: This retrospective cohort study used electronic health record data from 26 institutions participating in the National Patient-Centered Clinical Research Network from January 1, 2009, to December 31, 2016. Participant inclusion required at least 1 valid set of same-day height and weight measurements at each of the following age periods: 0 to 5, 6 to 11, 12 to 23, 24 to 59, and 60 to 131 months (183â¯444 children). Data were analyzed from June 1, 2019, to June 30, 2020. Exposures: Antibiotic use at 0 to 5, 6 to 11, 12 to 23, 24 to 35, and 36 to 47 months of age. Main Outcomes and Measures: Age and magnitude of BMI peak and BMI rebound. Results: Of 183â¯444 children in the study (mean age, 3.3 years [range, 0-10.9 years]; 95â¯228 [51.9%] were boys; 80â¯043 [43.6%] were White individuals), 78.1% received any antibiotic, 51.0% had at least 1 episode of broad-spectrum antibiotic exposure, and 65.0% had at least 1 episode of narrow-spectrum antibiotic exposure at any time before 48 months of age. Exposure to any antibiotics at 0 to 5 months of age (vs no exposure) was associated with later age (ß coefficient, 0.05 months [95% CI, 0.02-0.08 months]) and higher BMI (ß coefficient, 0.09 [95% CI, 0.07-0.11]) at peak. Exposure to any antibiotics at 0 to 47 months of age (vs no exposure) was associated with an earlier age (-0.60 months [95% CI, -0.81 to -0.39 months]) and higher BMI at rebound (ß coefficient, 0.02 [95% CI, 0.01-0.03]). These associations were strongest for children with at least 4 episodes of antibiotic exposure. Effect estimates for associations with age at BMI rebound were larger for those exposed to antibiotics at 24 to 35 months of age (ß coefficient, -0.63 [95% CI, -0.83 to -0.43] months) or 36 to 47 (ß coefficient, -0.52 [95% CI, -0.72 to -0.31] months) than for those exposed at 0 to 5 months of age (ß coefficient, 0.26 [95% CI, 0.01-0.51] months) or 6 to 11 (ß coefficient, 0.00 [95% CI, -0.20 to 0.20] months). Conclusions and Relevance: In this cohort study, antibiotic exposure was associated with statistically significant, but small, differences in BMI trajectory milestones in infancy and early childhood. The small risk of an altered BMI trajectory milestone pattern associated with early-life antibiotic exposure is unlikely to be a key factor during prescription decisions for children.