{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T16:16:53Z","timestamp":1780676213890,"version":"3.54.1"},"reference-count":69,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T00:00:00Z","timestamp":1760313600000},"content-version":"vor","delay-in-days":12,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Birth Defects Research"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Haloacetic acids (HAAs) are water disinfection byproducts (DBPs) regulated as a mixture of five species (HAA5) in the United States and Canada. To date, two brominated HAAs (BrHAAs) in HAA5 (monobromoacetic acid [MBAA], dibromoacetic acid [DBAA]) have been associated with birth defects in some epidemiologic studies, but the other four unregulated BrHAAs remain understudied.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We analyzed registry\u2010based case\u2013control data on 16 birth defect phenotypes in relation to temporally weighted first\u2010trimester exposures to the four unregulated BrHAAs (tribromoacetic acid [TBAA], bromochloroacetic acid [BCAA], bromodichloroacetic acid [BDCAA], chlorodibromoacetic acid [CDBAA]) and the sum of all six BrHAAs (HAA6\u2009=\u2009TBAA\u2009+\u2009BCAA\u2009+\u2009BDCAA\u2009+\u2009CDBAA\u2009+\u2009MBAA\u2009+\u2009DBAA). We matched cases to controls 1:10 on the week of conception and estimated adjusted odds ratios (aORs) via conditional logistic regression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We observed some elevated aORs for dichotomized BrHAA exposures with certain outcomes, such as cleft palate alone (BDCAA aOR\u2009=\u20091.75 [95% confidence interval: 1.15, 2.66]), ventricular septal defects (BDCAA aOR\u2009=\u20091.28 [0.97, 1.68]), tetralogy of Fallot (BDCAA OR\u2009=\u20091.57 [0.93, 2.64]), and obstructive genitourinary defects (CDBAA aOR\u2009=\u20091.65 [1.07, 2.53]), and reduced aORs for hypospadias (e.g., BCAA aOR\u2009=\u20090.58 [0.40, 0.84]). Most other associations were closer to the null, and many lacked precision.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our observations warrant further investigation given their novelty and the paucity of data on health impacts of prenatal BrHAA exposures overall; ours is the first epidemiological study to investigate most of these exposure\u2010outcome relationships. Future work would benefit from a longer study period to ascertain additional birth defect cases and more direct exposure assessment in areas served by water systems with higher bromide levels.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/bdr2.2537","type":"journal-article","created":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T01:38:44Z","timestamp":1760405924000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Risks of Birth Defects Following In Utero Exposures to Unregulated Brominated Haloacetic Acids"],"prefix":"10.1002","volume":"117","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4043-3180","authenticated-orcid":false,"given":"John A.","family":"Kaufman","sequence":"first","affiliation":[{"name":"Department of Epidemiology Rollins School of Public Health, Emory University  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Michael","family":"Wright","sequence":"additional","affiliation":[{"name":"Center for Public Health and Environmental Assessment, Office of Research and Development, U.S. Environmental Protection Agency  Cincinnati Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,10,13]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.15585\/mmwr.mm6902a1"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1177\/003335491112600209"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.23006"},{"issue":"1","key":"e_1_2_10_5_1","first-page":"1","article-title":"Update on Overall Prevalence of Major Birth Defects\u2014Atlanta, Georgia, 1978\u20102005","volume":"57","author":"Centers for Disease Control and Prevention (CDC)","year":"2008","journal-title":"MMWR. Morbidity and Mortality Weekly Report"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1289\/ehp.10980"},{"key":"e_1_2_10_7_1","volume-title":"Standard Methods for the Examination of Water and Wastewater","author":"Eaton A. D.","year":"1995"},{"issue":"11","key":"e_1_2_10_8_1","first-page":"1","article-title":"Infant Mortality in the United States, 2021: Data From the Period Linked Birth\/Infant Death File","volume":"72","author":"Ely D. M.","year":"2023","journal-title":"National Vital Statistics Reports"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.aje.a009610"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.est.4c10202"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0140\u20106736(21)01207\u20101"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jclinepi.2021.06.007"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.i1981"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwac091"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1097\/aog.0000000000003614"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/ppe.12650"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1080\/1047322X.1990.10389587"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.reprotox.2005.09.012"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/(sici)1096\u20109926(199606)54:2<57::Aid\u2010tera1>3.0.Co;2\u20101"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1186\/1476\u2010069x\u20107\u201023"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdr2.2370"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/tcm.10010"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1097\/jom.0000000000001191"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1097\/ee9.0000000000000081"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41370\u2010023\u201000595\u20101"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.sempedsurg.2022.151230"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1289\/ehp7961"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyu249"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1136\/oem.2007.034256"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41370\u2010023\u201000559\u20105"},{"key":"e_1_2_10_31_1","unstructured":"Ma X.2021.\u201cPrediction of the Formation Speciation and Health Risks of Unregulated Disinfection Byproducts in Drinking Water Using a Kinetic Binomial Model.\u201dCivil & Environmental Engineering University of Massachusetts Amherst.https:\/\/doi.org\/10.7275\/24412584."},{"key":"e_1_2_10_32_1","unstructured":"Massachusetts Center for Birth Defects Research and Prevention.2025.\u201cAbout the Birth Defects Monitoring Program.\u201dhttps:\/\/www.mass.gov\/info\u2010details\/about\u2010the\u2010birth\u2010defects\u2010monitoring\u2010program#:~:text=The%20MA%20Center%20for%20Birth with%20birth%20defects%20in%20Massachusetts."},{"key":"e_1_2_10_33_1","unstructured":"Massachusetts Water Resources Authority. n.d.\u201cUCMR (Unregulated Contaminant Monitoring Rule) Data: UCMR 4 Test Results (2018\u20102020) for Fully Supplied Communities.\u201dCited June 9 2025.https:\/\/www.mwra.com\/your\u2010water\u2010system\/drinking\u2010water\u2010quality\/ucmr\u2010unregulated\u2010contaminant\u2010monitoring\u2010rule\u2010data."},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1289\/ehp10207"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdr2.2391"},{"key":"e_1_2_10_36_1","volume-title":"The Developing Human: Clinically Oriented Embryology","author":"Moore K. P.","year":"2016"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.reprotox.2010.08.002"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdr2.2427"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.22427\/ROC-MGRAPH-12"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1289\/ehp.0900677"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1289\/ehp.10636"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.scitotenv.2023.162981"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/em.20585"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwy172"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.est.5b03547"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.analchem.1c04640"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1111\/ppe.12326"},{"key":"e_1_2_10_48_1","first-page":"1","volume-title":"Proceedings of the Symposium on Safe Drinking Water: Where Science Meets Policy, Carolina Environmental Program","author":"Singer P. C.","year":"2006"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1021\/es960504q"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1002\/tera.1420400506"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1002\/tera.1420460305"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdr2.1607"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2011.1823"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.envres.2020.110280"},{"key":"e_1_2_10_55_1","volume-title":"Method 502.2. Volatile Organic Compounds in Water by Purge and Trap Capillary Column Gas Chromatography With Photoionization and Electrolytic Conductivity Detectors in Series","author":"USEPA","year":"1989"},{"key":"e_1_2_10_56_1","volume-title":"Method 524.2. Measurement of Purgeable Organic Compounds in Water by Capillary Gas Column Chromatography\/Mass Spectrometry","author":"USEPA","year":"1992"},{"key":"e_1_2_10_57_1","volume-title":"Method 552.1. Determination of Haloacetic Acids and Dalapon in Drinking Water by Ion\u2010Exchange Liquid\u2010Solid Extraction and Gas Chromatography With an Electron Capture Detector","author":"USEPA","year":"1992"},{"key":"e_1_2_10_58_1","volume-title":"Method 551.1. Determination of Chlorination Disinfection Byproducts, Chlorinated Solvents, and Halogenated Pesticides\/Herbicides in Drinking Water by Liquid\u2010Liquid Extraction and Gas Chromatography Electron\u2010Capture Detection","author":"USEPA","year":"1995"},{"key":"e_1_2_10_59_1","volume-title":"Method 552.2. Determination of Haloacetic Acids and Dalapon in Drinking Water by Liquid\u2010Liquid Extraction, Derivation and Gas Chromatography With Electron\u2010Capture Detection","author":"USEPA","year":"1995"},{"key":"e_1_2_10_60_1","volume-title":"Method 552.3: Determination of Haloacetic Acids and Dalapon in Drinking Water by Liquid\u2010Liquid Microextraction, Derivatization, and Gas Chromatography With Electron Capture Detection","author":"USEPA","year":"2003"},{"key":"e_1_2_10_61_1","unstructured":"USEPA.2024a.\u201cFourth Unregulated Contaminant Monitoring Rule.\u201dCited May 8 2025 https:\/\/www.epa.gov\/dwucmr\/fourth\u2010unregulated\u2010contaminant\u2010monitoring\u2010rule."},{"key":"e_1_2_10_62_1","volume-title":"The Fourth Unregulated Contaminant Monitoring Rule (UCMR 4), Data Summary: 2018\u20132020","author":"USEPA","year":"2024"},{"key":"e_1_2_10_63_1","unstructured":"USEPA.2025.\u201cMonitoring Unregulated Contaminants in Drinking Water.\u201dCited 2025 May 8 2025.https:\/\/www.epa.gov\/dwucmr."},{"key":"e_1_2_10_64_1","doi-asserted-by":"publisher","DOI":"10.1289\/EHP2450"},{"key":"e_1_2_10_65_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdr2.1348"},{"key":"e_1_2_10_66_1","doi-asserted-by":"publisher","DOI":"10.1017\/S1466046612000427"},{"key":"e_1_2_10_67_1","doi-asserted-by":"publisher","DOI":"10.1289\/ehp103"},{"key":"e_1_2_10_68_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhazmat.2025.137833"},{"key":"e_1_2_10_69_1","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwac035"},{"key":"e_1_2_10_70_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijerph17249564"}],"container-title":["Birth Defects Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bdr2.2537","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/bdr2.2537","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bdr2.2537","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T09:42:36Z","timestamp":1779097356000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/bdr2.2537"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10]]},"references-count":69,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2025,10]]}},"alternative-id":["10.1002\/bdr2.2537"],"URL":"https:\/\/doi.org\/10.1002\/bdr2.2537","archive":["Portico"],"relation":{},"ISSN":["2472-1727","2472-1727"],"issn-type":[{"value":"2472-1727","type":"print"},{"value":"2472-1727","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10]]},"assertion":[{"value":"2025-07-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-03","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-13","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2537"}}