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3134 Organophosphate pesticide exposure during pregnancy, gestational weight gain and long-term postpartum weight retention
- Linda G Kahn, Elise M Philips, Michiel A van den Dries, Romy Gaillard, Susana Santos, Kelly Ferguson, Vincent V W Jaddoe, Leonardo Trasande
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- Journal:
- Journal of Clinical and Translational Science / Volume 3 / Issue s1 / March 2019
- Published online by Cambridge University Press:
- 26 March 2019, p. 50
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OBJECTIVES/SPECIFIC AIMS: Little is known about potentially obesogenic endocrine-disruptors’ effects on excessive gestational weight gain (GWG) and postpartum weight retention (PPWR), which increase risk of adverse pregnancy and postnatal outcomes. We explored associations between prenatal organophosphate (OP) pesticide exposure and increased weight both during and after pregnancy. METHODS/STUDY POPULATION: Three dimethyl (DM) and three diethyl (DE) OP metabolites were measured in spot urine samples collected at <18, 18-25, and >25 gestational weeks among 688 participants in the Generation R Study. Metabolite levels were expressed as molar concentration/gram creatinine and log10-transformed. GWG and PPWR were calculated as the difference between weight at each prenatal/postnatal visit or maximum gestational weight and pre-pregnancy weight. In covariate-adjusted regression models we assessed associations of metabolite concentrations at each prenatal visit and, where appropriate, averaged across pregnancy with early-to-mid pregnancy, mid-to-late pregnancy, late pregnancy-to-maximum, and total GWG; insufficient and excessive GWG according to Institute of Medicine guidelines; and long-term PPWR at 6 and 10 years postpartum. Based on OP pesticides’ lipophilicity and association with hypomethylation, we investigated interactions with pre-pregnancy body mass index, periconceptional folic acid supplementation, and breastfeeding duration. RESULTS/ANTICIPATED RESULTS: A 10-fold increase in late pregnancy DE metabolite concentration was associated with 1.34 kg [95% confidence interval: 0.55, 2.12] higher late pregnancy-to-maximum GWG. A 10-fold increase in mean DE metabolite concentration across pregnancy was associated with 2.41 kg [0.62, 4.20] lower PPWR at 6 years. Stratified analysis suggested that the prenatal finding was driven by women with pre-pregnancy BMI ≥25 kg/m2, while the postnatal finding was driven by women with pre-pregnancy BMI <25 kg/m2 and with inadequate folic acid supplementation. We found no associations between OP pesticide metabolites and insufficient or excessive weight gain and no interaction with breastfeeding. DISCUSSION/SIGNIFICANCE OF IMPACT: In this longitudinal analysis, we observed a positive association of OP pesticide metabolites with GWG in late pregnancy among overweight/obese women, potentially reflecting inhibition of OP pesticide detoxification by oxidative stress. Postnatally, under/normal weight women with higher OP pesticide metabolites had lower PPWR, possibly due to better metabolic function and a more healthful diet. These results suggest that there may be a critical period during the late phase of pregnancy when OP pesticide exposure may increase GWG, and this association may be amplified in overweight/obese women. Areas for future research include examination of how the interaction between OP pesticides and polymorphisms of the paraoxonase (PON1) gene, which detoxifies OP pesticides, affect GWG/PPWR; exploration of the interplay among maternal pre-pregnancy BMI, oxidative stress, and PON1 levels; and characterization of the variability of OP pesticides exposure across pregnancy using more frequent repeated urine samples.
Recommendations for Nanomedicine Human Subjects Research Oversight: An Evolutionary Approach for an Emerging Field
- Leili Fatehi, Susan M. Wolf, Jeffrey McCullough, Ralph Hall, Frances Lawrenz, Jeffrey P. Kahn, Cortney Jones, Stephen A. Campbell, Rebecca S. Dresser, Arthur G. Erdman, Christy L. Haynes, Robert A. Hoerr, Linda F. Hogle, Moira A. Keane, George Khushf, Nancy M. P. King, Efrosini Kokkoli, Gary Marchant, Andrew D. Maynard, Martin Philbert, Gurumurthy Ramachandran, Ronald A. Siegel, Samuel Wickline
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- Journal:
- Journal of Law, Medicine & Ethics / Volume 40 / Issue 4 / Winter 2012
- Published online by Cambridge University Press:
- 01 January 2021, pp. 716-750
- Print publication:
- Winter 2012
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Nanomedicine is yielding new and improved treatments and diagnostics for a range of diseases and disorders. Nanomedicine applications incorporate materials and components with nanoscale dimensions (often defined as 1-100 nm, but sometimes defined to include dimensions up to 1000 nm, as discussed further below) where novel physiochemical properties emerge as a result of size-dependent phenomena and high surface-to-mass ratio. Nanotherapeutics and in vivo nanodiagnostics are a subset of nanomedicine products that enter the human body. These include drugs, biological products (biologics), implantable medical devices, and combination products that are designed to function in the body in ways unachievable at larger scales. Nanotherapeutics and in vivo nanodiagnostics incorporate materials that are engineered at the nanoscale to express novel properties that are medicinally useful. These nanomedicine applications can also contain nanomaterials that are biologically active, producing interactions that depend on biological triggers. Examples include nanoscale formulations of insoluble drugs to improve bioavailability and pharmacokinetics, drugs encapsulated in hollow nanoparticles with the ability to target and cross cellular and tissue membranes (including the bloodbrain barrier) and to release their payload at a specific time or location, imaging agents that demonstrate novel optical properties to aid in locating micrometastases, and antimicrobial and drug-eluting components or coatings of implantable medical devices such as stents.