{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T01:12:20Z","timestamp":1793063540035,"version":"4.5.0"},"reference-count":71,"publisher":"American Medical Association (AMA)","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"<jats:sec id=\"ab-zoi230462-4\"><jats:title>Importance<\/jats:title><jats:p>Prenatal perfluoroalkyl and polyfluoroalkyl substances (PFAS) have been linked to adverse birth outcomes. Previous research showed that higher folate concentrations are associated with lower blood PFAS concentrations in adolescents and adults. Further studies are needed to explore whether prenatal folate status mitigates PFAS-related adverse birth outcomes.<\/jats:p><\/jats:sec><jats:sec id=\"ab-zoi230462-5\"><jats:title>Objective<\/jats:title><jats:p>To examine whether prenatal folate status modifies the negative associations between pregnancy PFAS concentrations, birth weight, and gestational age previously observed in a US cohort.<\/jats:p><\/jats:sec><jats:sec id=\"ab-zoi230462-6\"><jats:title>Design, Setting, and Participants<\/jats:title><jats:p>In a prospective design, a prebirth cohort of mothers or pregnant women was recruited between April 1999 and November 2002, in Project Viva, a study conducted in eastern Massachusetts. Statistical analyses were performed from May 24 and October 25, 2022.<\/jats:p><\/jats:sec><jats:sec id=\"ab-zoi230462-7\"><jats:title>Exposure<\/jats:title><jats:p>Plasma concentrations of 6 PFAS compounds were measured in early pregnancy (median gestational week, 9.6). Folate status was assessed through a food frequency questionnaire and measured in plasma samples collected in early pregnancy.<\/jats:p><\/jats:sec><jats:sec id=\"ab-zoi230462-8\"><jats:title>Main Outcomes and Measures<\/jats:title><jats:p>Birth weight and gestational age, abstracted from delivery records; birth weight <jats:italic>z<\/jats:italic> score, standardized by gestational age and infant sex; low birth weight, defined as birth weight less than 2500 g; and preterm birth, defined as birth at less than 37 completed gestational weeks.<\/jats:p><\/jats:sec><jats:sec id=\"ab-zoi230462-9\"><jats:title>Results<\/jats:title><jats:p>The cohort included a total of 1400 mother-singleton pairs. The mean (SD) age of the mothers was 32.21 (4.89) years. Most of the mothers were White (73.2%) and had a college degree or higher (69.1%). Early pregnancy plasma perfluorooctanoic acid concentration was associated with lower birth weight and birth weight <jats:italic>z<\/jats:italic> score only among mothers whose dietary folate intake (birth weight: \u03b2, \u221289.13 g; 95% CI, \u2212166.84 to \u221211.42 g; birth weight <jats:italic>z<\/jats:italic> score: \u22120.13; 95% CI, \u22120.26 to \u22120.003) or plasma folate concentration (birth weight: \u221287.03 g; 95% CI, \u2212180.11 to 6.05 g; birth weight <jats:italic>z<\/jats:italic> score: \u22120.14; 95% CI, \u22120.30 to 0.02) were below the 25th percentile (dietary: 660 \u03bcg\/d, plasma: 14 ng\/mL). No associations were found among mothers in the higher folate level groups, although the tests for heterogeneity did not reject the null. Associations between plasma perfluorooctane sulfonic acid and perfluorononanoate (PFNA) concentrations and lower birth weight, and between PFNA and earlier gestational age were noted only among mothers whose prenatal dietary folate intake or plasma folate concentration was in the lowest quartile range. No associations were found among mothers in higher folate status quartile groups.<\/jats:p><\/jats:sec><jats:sec id=\"ab-zoi230462-10\"><jats:title>Conclusions and Relevance<\/jats:title><jats:p>In this large, US prebirth cohort, early pregnancy exposure to select PFAS compounds was associated with  adverse birth outcomes only among mothers below the 25th percentile of prenatal dietary or plasma folate levels.<\/jats:p><\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2023.14934","type":"journal-article","created":{"date-parts":[[2023,5,31]],"date-time":"2023-05-31T15:33:18Z","timestamp":1685547198000},"page":"e2314934","source":"Crossref","is-referenced-by-count":46,"title":["Association of Early Pregnancy Perfluoroalkyl and Polyfluoroalkyl Substance Exposure With Birth Outcomes"],"prefix":"10.1001","volume":"6","author":[{"given":"Yu","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Environmental Health, Harvard T. H. 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Chan School of Public Health, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brent","family":"Coull","sequence":"additional","affiliation":[{"name":"Department of Environmental Health, Harvard T. H. Chan School of Public Health, Boston, Massachusetts"},{"name":"Department of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"McElrath","sequence":"additional","affiliation":[{"name":"Harvard Medical School, Boston, Massachusetts"},{"name":"Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts"},{"name":"Department of Obstetrics and Gynecology, Brigham and Women's Hospital, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheryl L.","family":"Rifas-Shiman","sequence":"additional","affiliation":[{"name":"Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leah","family":"Martin","sequence":"additional","affiliation":[{"name":"Department of Environmental Health, Harvard T. H. Chan School of Public Health, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Environmental Health, Harvard T. H. Chan School of Public Health, Boston, Massachusetts"},{"name":"Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Xin","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Environmental Health, Harvard T. H. Chan School of Public Health, Boston, Massachusetts"},{"name":"Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Oken","sequence":"additional","affiliation":[{"name":"Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, Massachusetts"},{"name":"Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andres","family":"Cardenas","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Population Health, Stanford University, Stanford, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Messerlian","sequence":"additional","affiliation":[{"name":"Department of Environmental Health, Harvard T. H. Chan School of Public Health, Boston, Massachusetts"},{"name":"Department of Epidemiology, Harvard T. H. 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