Katherine Tassiopoulos1, Yanling Huo2, Joseph Braun3, Paige L Williams4, Renee Smith5, Ann Aschengrau6, Sharon Nichols7, Rohan Hazra8, William A Meyer9, Katherine Knapp10, Nagamah S Deygoo11, George R Seage Iii12. 1. Harvard T.H. Chan School of Public Health, Epidemiology , 677 Huntington Avenue , Kresge 817B , Boston, Massachusetts, United States , 02115 ; ktassiop@hsph.harvard.edu. 2. Center for Biostatistics in AIDS Research, Boston, Massachusetts, United States ; yhuo@sdac.harvard.edu. 3. Brown University School of Public Health, 174610, Epidemiology, Providence, Rhode Island, United States ; joseph_braun_1@brown.edu. 4. Harvard School of Public Health, Biostatistics, Boston, Massachusetts, United States ; paige@sdac.harvard.edu. 5. University of Illinois, Chicago, Pediatrics, Chicago, Illinois, United States ; resmith@uic.edu. 6. Boston University School of Public Health, Epidemiology, Boston, Massachusetts, United States ; aaschen@bu.edu. 7. University of California, San Diego, Neurosciences, San Diego, California, United States ; slnichols@ucsd.edu. 8. National Institutes of Health, 2511, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland, United States ; hazrar@mail.nih.gov. 9. Quest Diagnostics, Laboratory Operations, Baltimore, Maryland, United States ; William.A.Meyer@questdiagnostics.com. 10. St. Jude Children's Research Hospital, Infectious Diseases, Memphis, Tennessee, United States ; Katherine.Knapp@STJUDE.ORG. 11. NYU School of Medicine, Pediatrics, New York, New York, United States ; Nagamah.Deygoo@nyumc.org. 12. Epidemiology, Boston, Massachusetts, United States ; gseage@hsph.harvard.edu.
Abstract
BACKGROUND: While children's exposure to environmental lead in the U.S. has decreased, areas of elevated levels remain. Because lead exposure is a risk factor for developmental delays, it should be considered when studying neurodevelopmental effects of in-utero antiretroviral medication (ARV) exposure in the growing population of perinatally HIV-exposed, uninfected children (PHEU). We compared blood lead levels (BPb) in PHEU children enrolled in the Surveillance Monitoring of ART Toxicities (SMARTT) Study to U.S. children, assessed associations with neurodevelopment, and explored whether associations between in-utero ARV and neurodevelopment are modified by BPb. METHODS: Prevalence of elevated BPb (≥5 µg/dL) at ages 1-2 years was calculated by year and race/ethnicity and compared to that for children in the National Health and Nutrition Examination Survey (NHANES 2002-2010). Associations between elevated BPb and neurodevelopment at 1 and 3 years were assessed. Associations between ARVs (tenofovir disopropil fumarate [TDF]; atazanavir) and neurodevelopment were evaluated within BPb level (≥5 vs. <5 µg/dL). RESULTS: Mean BPb in SMARTT decreased from 5.9 to 2.7 µg/dL between 1998-2014; prevalence of elevated BPb decreased from 50% to 4%. Both were consistently higher than in NHANES. Elevated BPb was associated with cognitive delay at age 3 (adjusted odds ratio: 1.64; 95% CI: 0.95, 2.90). At age 1, TDF was associated with delay only among those with elevated BPb. CONCLUSIONS: PHEU children more often had elevated BPb than the general U.S. pediatric population. Exposure to environmental lead is one of several factors that may place these children at higher risk for neurodevelopmental delay.
BACKGROUND: While children's exposure to environmental lead in the U.S. has decreased, areas of elevated levels remain. Because lead exposure is a risk factor for developmental delays, it should be considered when studying neurodevelopmental effects of in-utero antiretroviral medication (ARV) exposure in the growing population of perinatally HIV-exposed, uninfected children (PHEU). We compared blood lead levels (BPb) in PHEU children enrolled in the Surveillance Monitoring of ART Toxicities (SMARTT) Study to U.S. children, assessed associations with neurodevelopment, and explored whether associations between in-utero ARV and neurodevelopment are modified by BPb. METHODS: Prevalence of elevated BPb (≥5 µg/dL) at ages 1-2 years was calculated by year and race/ethnicity and compared to that for children in the National Health and Nutrition Examination Survey (NHANES 2002-2010). Associations between elevated BPb and neurodevelopment at 1 and 3 years were assessed. Associations between ARVs (tenofovir disopropil fumarate [TDF]; atazanavir) and neurodevelopment were evaluated within BPb level (≥5 vs. <5 µg/dL). RESULTS: Mean BPb in SMARTT decreased from 5.9 to 2.7 µg/dL between 1998-2014; prevalence of elevated BPb decreased from 50% to 4%. Both were consistently higher than in NHANES. Elevated BPb was associated with cognitive delay at age 3 (adjusted odds ratio: 1.64; 95% CI: 0.95, 2.90). At age 1, TDF was associated with delay only among those with elevated BPb. CONCLUSIONS: PHEU children more often had elevated BPb than the general U.S. pediatric population. Exposure to environmental lead is one of several factors that may place these children at higher risk for neurodevelopmental delay.
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